\u5fae\u536b\u661f\u4e0d\u7a33\u5b9a\u6027(microsatellite instability,MSI)\u662fDNA\u590d\u5236\u8fc7\u7a0b\u4e2d\u5f62\u6210\u5927\u91cf\u79fb\u7801\u7a81\u53d8\u3001\u5f15\u8d77\u7684\u6838\u82f7\u9178\u91cd\u590d\u5355\u5143\u6570\u91cf\u6539\u53d8\u7684\u73b0\u8c61\uff0c\u591a\u79cd\u80bf\u7624\u4e2d\u5747\u53ef\u89c1MSI,\u5e38\u89c1\u4e8e\u7ed3\u76f4\u80a0\u764c\u3001\u5b50\u5bab\u5185\u819c\u764c\u548c\u80c3\u764c\u3002MSI\u68c0\u6d4b\u5bf9\u591a\u79cd\u5b9e\u4f53\u7624\u60a3\u8005\u6709\u91cd\u8981\u610f\u4e49\uff0c\u5305\u62ec\u6797\u5947\u7efc\u5408\u5f81\u7b5b\u67e5\u3001\u6307\u5bfc5-FU\u7c7b\u5316\u7597\u836f\u7269\u7684\u9009\u62e9\u3001\u9884\u540e\u5206\u5c42\u548c\u7b5b\u9009\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u83b7\u76ca\u4eba\u7fa4\u7b49\u3002\u76ee\u524d\uff0cMSI\u68c0\u6d4b\u4e3b\u8981\u5305\u62ecPCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6cd5\u3001PCR \u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u548cNGS\u6cd5\uff0c\u5176\u4e2d\u4ee5PCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6cd5\u4e3a\u91d1\u6807\u51c6\u3002\u672c\u6587\u57fa\u4e8e3\u79cd\u5e38\u7528\u7684\u6280\u672f\u5e73\u53f0\u5e76\u7ed3\u5408\u4e34\u5e8a\u5de5\u4f5c\u7ecf\u9a8c\uff0c\u5bf9MSI\u76f8\u5173\u673a\u5236\u3001\u68c0\u6d4b\u65b9\u6cd5\u548c\u8d28\u91cf\u63a7\u5236\u7b49\u8fdb\u884c\u9610\u8ff0\uff0c\u4ee5\u8fdb\u4e00\u6b65\u6307\u5bfc\u4e0e\u89c4\u8303\u6211\u56fdMSI\u7684\u68c0\u6d4b\u5de5\u4f5c\u3002<\/p>\n
1MSI\u7684\u6982\u5ff5<\/p>\n
\u5fae\u536b\u661f\u662f\u5b58\u5728\u4e8e\u539f\u6838\u751f\u7269\u548c\u771f\u6838\u751f\u7269\u7684\u57fa\u56e0\u7ec4\u4e2d\uff0c\u901a\u5e38\u75311~6\u4e2a\u78b1\u57fa\u5bf9\u7ec4\u6210\u7684DNA\u4e32\u8054\u91cd\u590d\u5e8f\u5217\uff0c\u5176\u53c8\u88ab\u79f0\u4f5c\u7b80\u5355\u91cd\u590d\u5e8f\u5217\u6216\u77ed\u4e32\u8054\u91cd\u590d\u5e8f\u5217,\u5e38\u89c1\u7c7b\u578b\u5305\u62ec\u5355\u6838\u82f7\u9178\u91cd\u590d\u3001\u4e8c\u6838\u82f7\u9178\u91cd\u590d\u3001\u4e09\u6838\u82f7\u9178\u91cd\u590d\u6216\u56db\u6838\u82f7\u9178\u91cd\u590d\u7b49\u3002\u5fae\u536b\u661f\u7684\u591a\u6001\u6027\u4e3b\u8981\u7531\u6838\u5fc3\u533a\u91cd\u590d\u5e8f\u5217\u7684\u62f7\u8d1d\u6570\u5dee\u5f02\u5f15\u8d77\uff0c\u5728\u4e00\u7c7b\u91cd\u590d\u5e8f\u5217\u4e2d1\u4e2a\u7279\u5b9a\u5e8f\u5217\u91cd\u590d\u7684\u4e30\u5ea6\u53ef\u80fd\u6709\u8f83\u5927\u5dee\u5f02\uff0c\u5982\u5728\u5355\u6838\u82f7\u9178\u91cd\u590d\u7684\u60c5\u51b5\u4e0b\uff0cpoly(A)\u6216poly(T)\u7684\u5bc6\u5ea6\u6bd4poly(G)\u6216poly(C)\u7684\u5bc6\u5ea6\u5927300\u500d\u3002\u5728\u4e8c\u6838\u82f7\u9178\u91cd\u590d\u5e8f\u5217\u4e2d\uff0cAC\u548cAT\u8f83\u591a\uff0cCG\u6700\u5c11\u3002\u7531\u4e8eDNA\u9519\u914d\u4fee\u590d(mismatch repair,MMR)\u57fa\u56e0\u7684\u7a81\u53d8\u6216\u8868\u89c2\u9057\u4f20\u53d1\u751f\u53d8\u5316\uff0cDNA MMR\u7cfb\u7edf\u7684\u6b63\u5e38\u529f\u80fd\u88ab\u7834\u574f\u3001\u5fae\u536b\u661f\u78b1\u57fa\u5bf9\u6570\u91cf\u53d1\u751f\u6539\u53d8\u79f0\u4e3aMSI\u3002\u5fae\u536b\u661f\u4f5c\u4e3a\u91cd\u8981\u7684\u5e8f\u5217\u7ec4\u6210\u90e8\u5206\uff0c\u5728\u57fa\u56e0\u7ec4\u8c03\u63a7\u4e2d\u53d1\u6325\u591a\u79cd\u4f5c\u7528\u3002\u5fae\u536b\u661fDNA\u591a\u6837\u6027\uff0c\u662f\u6784\u6210\u4eba\u7c7b\u57fa\u56e0\u7ec4\u591a\u6837\u6027\u7684\u5206\u5b50\u673a\u5236\u4e4b\u4e00\u3002<\/p>\n
2MSI\u7684\u53d1\u5c55\u53f2<\/p>\n
1984\u5e74\uff0c\u82f1\u56fd\u83b1\u65af\u7279\u5927\u5b66\u53d1\u73b0\u4eba\u7c7b\u808c\u7ea2\u86cb\u767d\u57fa\u56e0\u4e2d\u5b58\u5728\u591a\u6001GGAT\u91cd\u590d\u5e8f\u5217\u30021989\u5e74\uff0c\u7531Litt\u548cLuty\u9996\u6b21\u63d0\u51fa\u201c\u5fae\u536b\u661f\u201d\u7684\u6982\u5ff5\uff08\u56fe1)\u3002\u5fae\u536b\u661f\u662f\u77ed\u800c\u91cd\u590d\u7684DNA\u5e8f\u5217\uff0c\u5177\u6709\u5206\u5e03\u5e7f\u6cdb\u3001\u975e\u968f\u673a\u7684\u7279\u70b9\uff0c\u7ea6\u5360\u4eba\u7c7b\u57fa\u56e0\u7ec4\u76843%,\u4e3b\u8981\u5206\u5e03\u5728\u57fa\u56e0\u7684\u975e\u7f16\u7801\u533a\u548c\u67d3\u8272\u4f53\u672b\u7aef\u3002\u5728\u771f\u6838\u751f\u7269\u4e2d\uff0c\u9ad8\u4fdd\u771f\u7684DNA\u590d\u5236\u5bf9\u7ef4\u6301\u7ec6\u80de\u57fa\u56e0\u7ec4\u7a33\u5b9a\u6027\u548c\u6b63\u5e38\u751f\u7406\u529f\u80fd\u81f3\u5173\u91cd\u8981\uff0c\u4f46\u57fa\u56e0\u590d\u5236\u8fc7\u7a0b\u4e2d\u53d7\u73af\u5883\u56e0\u7d20\u7b49\u5f71\u54cd\uff0c\u6613\u53d1\u751f\u6838\u82f7\u9178\u7684\u9519\u8bef\u63ba\u5165\u6216\u7f3a\u5931\uff0c\u5f15\u8d77\u57fa\u56e0\u7ec4\u4e2d\u91cd\u590d\u5e8f\u5217\u6b21\u6570\u7684\u589e\u52a0\u6216\u4e22\u5931\u3002\u5728DNA\u805a\u5408\u9176\u548c\u591a\u79cd\u4fee\u590d\u673a\u5236\u7684\u57fa\u7840\u4e0a\uff0c\u4e00\u822c\u60c5\u51b5\u4e0bDNA\u590d\u5236\u7684\u9519\u8bef\u4f1a\u88ab\u4fee\u590d\u3002\u7136\u800c\uff0c\u5f53\u4f5c\u4e3a\u9ad8\u4fdd\u771fDNA\u590d\u5236\u6700\u540e\u4e00\u9053\u9632\u7ebf\u7684MMR\u7cfb\u7edf\u51fa\u73b0\u542f\u52a8\u5b50\u8d85\u7532\u57fa\u5316\u6216\u57fa\u56e0\u7a81\u53d8\u65f6\uff0cDNA\u590d\u5236\u9519\u8bef\u65e0\u6cd5\u7ea0\u6b63\u5e76\u8fde\u7eed\u79ef\u7d2f\uff0c\u5fae\u536b\u661f\u7684\u5e8f\u5217\u957f\u5ea6\u6216\u78b1\u57fa\u7ec4\u6210\u53d1\u751f\u53d8\u5316\u79f0\u4e3aMSI,\u4f7f\u57fa\u56e0\u7ec4\u8868\u73b0\u9ad8\u7a81\u53d8\u8868\u578b\u3002<\/p>\n<\/p>\n
1993\u5e74\uff0c\u7814\u7a76\u8005\u53d1\u73b0\u5728\u9057\u4f20\u6027\u975e\u606f\u8089\u75c5\u7ed3\u76f4\u80a0\u764c(hereditary non-polyposis colorectal cancer,HNPCC)\u4e2dMSI\u7684\u53d1\u751f\u7387\u9ad8\u8fbe86%,\u800c\u5728\u6563\u53d1\u6027\u7ed3\u76f4\u80a0\u764c\u4e2dMSI\u7684\u53d1\u751f\u7387\u4e5f\u8fbe16%\u3002\u4e0e\u6b64\u540c\u65f6\uff0c\u9646\u7eed\u6709\u7814\u7a76\u8005\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u53d1\u73b0\u7c7b\u4f3c\u5206\u5b50\u73b0\u8c61\uff0c\u4e0eMMR\u7cfb\u7edf\u529f\u80fd\u7f3a\u9677\u5bc6\u5207\u76f8\u5173\uff0c\u5f71\u54cd\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u7684\u751f\u5b58\u65f6\u95f4\u30021997\u5e74\uff0c\u7f8e\u56fd\u56fd\u5bb6\u764c\u75c7\u7814\u7a76\u6240(National Cancer Institute,NCI)\u5728\u7ed3\u76f4\u80a0\u764c\u7684\u56fd\u9645\u4e13\u9898\u4f1a\u8bae\u4e0a\uff0c\u5bf9MSI\u8fdb\u884c\u7edf\u4e00\u5b9a\u4e49\uff0c\u5373\u4e0e\u6b63\u5e38\u7ec4\u7ec7\u76f8\u6bd4\uff0c\u80bf\u7624\u7ec4\u7ec7\u4e2d\u7531\u5fae\u536b\u661f\u91cd\u590d\u5355\u5143\u7684\u63d2\u5165\u6216\u7f3a\u5931\u5bfc\u81f4\u7684\u5fae\u536b\u661f\u957f\u5ea6\u6539\u53d8\u79f0\u4e3aMSI\u3002\u540c\u5e74\uff0c\u7f8e\u56fdNCI\u5728MSI\u7814\u8ba8\u4f1a\u5bf9MSI\u68c0\u6d4b\u4f4d\u70b9\u7684\u9009\u62e9\u548c\u8bca\u65ad\u6807\u51c6\u8fdb\u884c\u89c4\u8303\u548c\u7edf\u4e00\uff0c\u63a8\u8350\u4e86\u7b80\u79f0\u4e3a\u201c2B3D\u201d\u7684MSI\u4f4d\u70b9\u68c0\u6d4bPanel,\u79f0\u4e4b\u4e3aBethesda Panel\u6216NCI Panel,\u8be5Panel\u5305\u62ec2\u4e2a\u5355\u6838\u82f7\u9178\u4f4d\u70b9(BAT-25\u548cBAT-26)\u548c3\u4e2a\u53cc\u6838\u82f7\u9178\u4f4d\u70b9(D2S123\u3001D5S346\u548cD17S250)\u3002\u540c\u65f6\uff0c\u4e13\u5bb6\u7ec4\u4e5f\u5236\u5b9aPanel\u5224\u8bfb\u6807\u51c6\uff1a\u82e55\u4e2a\u5fae\u536b\u661f\u4f4d\u70b9\u4e2d\u67092\u4e2a\u62162\u4e2a\u4ee5\u4e0a\u7684\u5fae\u536b\u661f\u4f4d\u70b9\u4e0d\u7a33\u5b9a\uff0c\u5219\u4e3a\u5fae\u536b\u661f\u9ad8\u5ea6\u4e0d\u7a33\u5b9a\u6027(microsatellitein stability-high,MSI-H);\u82e5\u67091\u4e2a\u5fae\u536b\u661f\u4f4d\u70b9\u4e0d\u7a33\u5b9a\uff0c\u5219\u4e3a\u5fae\u536b\u661f\u4f4e\u5ea6\u4e0d\u7a33\u5b9a\u6027(microsatellite instability-low,MSI-L);\u82e55\u4e2a\u5fae\u536b\u661f\u4f4d\u70b9\u5747\u7a33\u5b9a\uff0c\u5219\u4e3a\u5fae\u536b\u661f\u7a33\u5b9a(microsatellite stability,MSS)\u30022002\u5e74\uff0c\u7f8e\u56fdNCI\u5bf9MSI\u7684\u68c0\u6d4b\u8fdb\u884c\u4fee\u8ba2\u548c\u8865\u5145\uff0c\u63a8\u8350\u542b\u67095\u4e2a\u5355\u6838\u82f7\u9178\u4f4d\u70b9(BAT-25\u3001BAT-26\u3001NR-21\u3001NR-22\u548cNR-24)\u6784\u6210\u7684Pentaplex Panel,\u68c0\u6d4b\u7075\u654f\u5ea6\u8fdc\u9ad8\u4e8e\u201c2B3D\u201dNCIPanel\u30022004\u5e74\uff0c\u7f8e\u56fdPromega\u516c\u53f8\u53d1\u5e03\u5168\u7403\u9996\u4e2a\u5546\u54c1\u5316MSI\u68c0\u6d4b\u8bd5\u5242\u76d2\uff1b2006\u5e74\uff0cPromega Panel MSI\u68c0\u6d4b\u4f53\u7cfb\u51fa\u73b0\uff0c\u5c06Pentaplex Panel\u4e2d\u7684NR-22\u66ff\u6362\u4e3aMONO-27,\u5305\u62ec5\u4e2a\u5355\u6838\u82f7\u9178\u4f4d\u70b9(BAT-25\u3001BAT-26\u3001NR-21\u3001MONO-27\u548cNR-24)\u548c2\u4e2a\u5bf9\u7167\u4f4d\u70b9(PentaC\u3001PentaD)\u3002\u76ee\u524d\uff0c\u56fd\u5185\u5916\u6743\u5a01\u6307\u5357\u548c\u4e13\u5bb6\u5171\u8bc6\u63a8\u8350MSI\u68c0\u6d4b\u65b9\u6cd5\u4e3b\u8981\u662f2B3D Panel\u548cPromega Panel\u3002<\/p>\n
2015~2017\u5e74\uff0c\u5927\u91cf\u4e34\u5e8a\u7814\u7a76\u8bc1\u5b9ePD-1\/PD-L1\u6291\u5236\u5242\u5bf9MSI-H\/\u9519\u914d\u4fee\u590d\u529f\u80fd\u7f3a\u9677(deficient mismatch repair,dMMR)\u5b9e\u4f53\u7624\u60a3\u8005\u7597\u6548\u663e\u8457\u30022017\u5e74\uff0c\u7f8e\u56fd\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40(Food and Drug Administration,FDA)\u6b63\u5f0f\u6279\u51c6\u5e15\u535a\u5229\u73e0\u5355\u6297\u7528\u4e8eMSI-H\u578b\u665a\u671f\u6216\u8f6c\u79fb\u6027\u5b9e\u4f53\u7624\u60a3\u8005\u7684\u6cbb\u7597\u3002\u76ee\u524d\uff0cMSI-H\u53d1\u751f\u7387\u9ad8\u7684\u5b9e\u4f53\u7624\u5305\u62ec\u5b50\u5bab\u5185\u819c\u764c(20%~30%)\u3001\u80c3\u764c(15%~20%)\u548c\u7ed3\u76f4\u80a0\u764c(12%~15%)\u3002\u4e2d\u56fd\u6bcf\u5e74\u65b0\u589eMSI-H\u60a3\u8005\u4eba\u6570\u8fd130\u4e07\uff0c\u7f8e\u56fd\u56fd\u7acb\u7efc\u5408\u764c\u75c7\u7f51\u7edc(National Comprehensive Cancer Network,NCCN)\u6216\u4e2d\u56fd\u4e34\u5e8a\u80bf\u7624\u5b66\u4f1a(Chinese Society of Clinical Oncology,CSCO)\u7684\u6700\u65b0\u6307\u5357\uff0c\u5c06MSI\u68c0\u6d4b\u4f5c\u4e3a\u7ed3\u76f4\u80a0\u764c\u3001\u5b50\u5bab\u5185\u819c\u764c\u3001\u5c0f\u80a0\u817a\u764c\u548c\u80c3\u764c\u4e00\u7ebf\u6cbb\u7597\u65b9\u6848\u7684\u5fc5\u8981\u68c0\u6d4b\u3002\u6b64\u5916\uff0c\u884c\u6797\u5947\u7efc\u5408\u5f81\u7b5b\u67e5\u548c\u63a5\u53d7\u514d\u75ab\u6cbb\u7597\u7684\u5b9e\u4f53\u7624\u60a3\u8005\u5747\u63a8\u8350\u884cMSI\u68c0\u6d4b\u3002<\/p>\n
3MSI\u7684\u81f4\u75c5\u673a\u5236(MMR\u673a\u5236\uff09<\/p>\n
3.1MMR\u7ec4\u6210\u4e0e\u529f\u80fd<\/p>\n
1964\u5e74\uff0cMMR\u7cfb\u7edf\u9610\u8ff0\u4e86\u7ec6\u83cc\u548c\u9175\u6bcd\u4e2d\u7684DNA\u5207\u9664\uff0d\u518d\u5408\u6210\u8fc7\u7a0b\uff0c\u4e3b\u8981\u7ea0\u6b63\u5728DNA\u4e2d\u4ea7\u751f\u7684\u9519\u914d\u6838\u82f7\u9178\u6216\u63d2\u5165\uff0d\u7f3a\u5931\u73af\u7684\u590d\u5236\u9519\u8bef\u3002MMR\u57fa\u56e0\u7684\u4ea7\u7269\u662fMMR\u86cb\u767d\uff0c\u5c5e\u4e8e\u6838\u9178\u6c34\u89e3\u9176\u3002DNA\u5728\u590d\u5236\u8fc7\u7a0b\u4e2d\u4f1a\u4e0d\u53ef\u907f\u514d\u5730\u53d1\u751f\u9519\u8bef\uff0c\u800cMMR\u7cfb\u7edf\u8d77\u5230\u8d1f\u8d23\u76d1\u89c6\u548c\u4fee\u6b63DNA\u590d\u5236\u548c\u91cd\u7ec4\u8fc7\u7a0b\u4e2d\u7684\u9519\u8bef\uff0c\u4f7fDNA\u80fd\u7cbe\u786e\u590d\u5236\uff0c\u4fdd\u8bc1\u9057\u4f20\u7684\u4fdd\u5b88\u6027\u548c\u7a33\u5b9a\u6027\u3002<\/p>\n
MMR\u7cfb\u7edf\u5e7f\u6cdb\u5b58\u5728\u4e8e\u751f\u7269\u4f53\u5185\uff0c\u5728\u5927\u80a0\u57c3\u5e0c\u83cc(esche-richia coli, E .coli)\u4e2d\u53d1\u73b0MMR,\u5373MutSLH\u4f9d\u8d56\u4e8eMutS\u3001MutL\u3001MutH\u7b49\u57fa\u56e0\u7f16\u7801\u7684\u4ea7\u7269\u3002\u5728E.coli\u7684DNA\u590d\u5236\u8fc7\u7a0b\u4e2d\uff0c\u65b0\u751f\u94fe\u4e0a\u7ea6256\u4e2a\u78b1\u57fa\u5bf9\u51fa\u73b01\u6b21GATC\u5e8f\u5217\uff0c\u5728\u88ab\u5408\u6210\u540e\u7684\u77ed\u65f6\u95f4\u5185\u4e0d\u4f1a\u88ab\u7532\u57fa\u5316\uff0c\u800c\u6b64\u65f6\u6a21\u677f\u94fe\u4e0a\u7684GATC\u5e8f\u5217\u5df2\u88ab\u7532\u57fa\u5316\u3002\u8be5\u5dee\u5f02\u4f7f\u6a21\u677f\u94fe\u4e0e\u65b0\u751f\u94fe\u6682\u65f6\u5f97\u4ee5\u533a\u5206\uff0c\u4e3aMutSLH-MMR\u7279\u5f02\u6027\u8bc6\u522b\u63d0\u4f9b\u524d\u63d0\u548c\u57fa\u7840\u3002MutS\u8bc6\u522b\u9519\u914d\u6216\u672a\u914d\u5bf9\u78b1\u57fa\u5e76\u4e0e\u4e4b\u7ed3\u5408\uff0cMutL\u53c2\u4e0e\u5f62\u6210\u590d\u5408\u4f53\u201cMutL-MutS-DNA\u201d,\u5e76\u6fc0\u6d3bMutH\u7684\u6838\u9178\u5185\u5207\u9176\u6d3b\u6027\uff0c\u5728\u9519\u914d\u4f4d\u70b9\u9644\u8fd1(GATC)\u5e8f\u5217\u5904\u5c06\u975e\u7532\u57fa\u5316\u7684DNA\u94fe\u5207\u5272\uff0c\u7136\u540e\u6838\u9178\u5916\u5207\u9176\u5728\u89e3\u87ba\u65cb\u9176\u548c\u5355\u94feDNA\u7ed3\u5408\u86cb\u767d\u7684\u534f\u52a9\u4e0b\uff0c\u5c06\u975e\u7532\u57fa\u5316\u7684DNA\u5e8f\u5217\u4eceGATG\u4f4d\u70b9\u81f3\u9519\u914d\u4f4d\u70b9\u6574\u6bb5\u53bb\u9664\u3002<\/p>\n
\u76ee\u524d\uff0c\u771f\u83cc\u548c\u54fa\u4e73\u52a8\u7269\u4f53\u5185\u7684MMR\u7cfb\u7edf\u4e5f\u5f00\u59cb\u5f97\u5230\u8fdb\u4e00\u6b65\u63a2\u7d22\u3002\u7814\u7a76\u53d1\u73b0\u591a\u4e2aMMR\u76f8\u5173\u5206\u5b50\uff0c\u4e3b\u8981\u5305\u62ec5\u4e2aMutS\u540c\u6e90\u4f53(MSH2\u3001MSH3\u3001MSH4\u3001MSH5\u3001MSH6)\u30014\u4e2aMutL\u540c\u6e90\u4f53(MLH1\u3001MLH2\/PMS1\u3001MLH3\u3001MLH4\/PMS2)\u3001MutH\u540c\u6e90\u4f53\u548cUvrD\u540c\u6e90\u4f53\u3002\u4eba\u7c7bMMR\u7cfb\u7edf\u4e2d\u7684\u4e3b\u8981\u86cb\u767d\u5305\u62ecMLH1\u3001MSH2\u3001MSH3\u3001MSH6\u3001PMS1\u3001PMS2\u548cMLH3,\u5b83\u4eec\u4ee5\u5f02\u6e90\u4e8c\u805a\u4f53\u7684\u5f62\u5f0f\u76f8\u4e92\u4f5c\u7528\u3002MSH2\u4e0eMSH6\u6216MSH3\u5076\u8054\uff08\u5206\u522b\u5f62\u6210MutS\u03b1\u548cMutS\u03b2\u590d\u5408\u7269\uff09\uff0c2\u4e2a\u5f02\u6e90\u4e8c\u805a\u4f53\u5747\u53ef\u8bc6\u522b\u65b0\u5408\u6210\u7684DNA\u6838\u82f7\u9178\u94fe\u4e0a\u7684\u78b1\u57fa\u9519\u914d\uff0c\u5e76\u4e0e\u9519\u914d\u4f4d\u70b9\u7ed3\u5408\uff1bMLH1\u4e0ePMS2\u3001PMS1\u6216MLH3\u5076\u8054\uff08\u5206\u522b\u5f62\u6210MutL\u03b1\u3001MutL\u03b2\u6216MutL\u03b3\u590d\u5408\u7269\uff09\uff0c\u4e0e\u7ed3\u5408\u5230DNA\u94fe\u4e0a\u7684MutS\u03b1\u6216MutS\u03b2\u5f62\u6210\u6682\u65f6\u6027\u7684\u590d\u5408\u7269\u542f\u52a8MMR,\u4e0e\u6709\u5173\u7684\u9176\u76f8\u4e92\u914d\u5408\uff0c\u5207\u9664\u542b\u6709\u9519\u914d\u78b1\u57fa\u76841\u6bb5DNA\u94fe\uff0c\u4ee5\u4ee3\u66ff\u88ab\u5207\u9664\u7684DNA\u94fe\uff0c\u5b8c\u6210\u542b\u9519\u914d\u78b1\u57faDNA\u6838\u9178\u94fe\u7684\u4fee\u590d\uff08\u56fe2)\u3002<\/p>\n<\/p>\n
3.2MMR\u4e0eMSI\u7684\u5173\u7cfb<\/p>\n
\u5fae\u536b\u661f\u5e8f\u5217\u662fDNA\u590d\u5236\u8fc7\u7a0b\u4e2d\u6700\u6613\u53d1\u751f\u9519\u914d\u7684\u5e8f\u5217\uff0c\u9700\u8981MMR\u76f8\u5173\u86cb\u767d\u4fee\u590d\u3002MMR\u662f\u9ad8\u5ea6\u4fdd\u5b88\u7684\u7ec6\u80de\u8fc7\u7a0b\uff0c\u5728DNA\u590d\u5236\u8fc7\u7a0b\u4e2d\u8d77\u91cd\u8981\u4f5c\u7528\u3002\u6709\u7814\u7a76\u8bc1\u5b9e\uff0cMMR\u4f7fDNA\u590d\u5236\u7684\u51c6\u786e\u6027\u63d0\u9ad8100~1000\u500d\u3002\u82e5MMR\u529f\u80fd\u7f3a\u9677\uff0c\u5fae\u536b\u661f\u51fa\u73b0\u7684\u590d\u5236\u9519\u8bef\u5f97\u4e0d\u5230\u7ea0\u6b63\u5e76\u4e0d\u65ad\u7d2f\u79ef\uff0c\u4f7f\u5fae\u536b\u661f\u5e8f\u5217\u957f\u5ea6\u6216\u78b1\u57fa\u7ec4\u6210\u53d1\u751f\u6539\u53d8\u79f0\u4e3aMSI\u3002\u540c\u65f6\uff0c\u5bfc\u81f4\u57fa\u56e0\u7ec4\u5448\u9ad8\u7a81\u53d8\u8868\u578b\uff0c\u5373MSI\u662fMMR\u7f3a\u9677\u5bfc\u81f4\u7684\u7ed3\u679c\uff0c\u6545\u53ef\u901a\u8fc7\u68c0\u6d4bMMR\u86cb\u767d\u7f3a\u5931\u53cd\u6620MSI\u72b6\u6001\u3002\u91c7\u7528\u514d\u75ab\u7ec4\u5316\u6cd5\u68c0\u6d4b\u80bf\u7624\u6837\u672c\u4e2dMLH1\u3001MSH2\u3001MSH6\u548cPMS2\u8868\u8fbe\uff0c\u82e54\u4e2aMMR\u86cb\u767d\u5747\u9633\u6027\uff0c\u5219\u4e3a\u9519\u914d\u4fee\u590d\u529f\u80fd\u5b8c\u6574(mis-match repair proficient, pMMR);\u4efb\u4e00MMR\u86cb\u767d\u7f3a\u5931\u5373\u4e3adMMR\u3002\u901a\u5e38dMMR\u76f8\u5f53\u4e8eMSI-H\u8868\u578b\uff0cpMMR\u76f8\u5f53\u4e8eMSI-L\/MSS\u8868\u578b\uff0c\u6839\u636e\u514d\u75ab\u7ec4\u5316\u68c0\u6d4b\u7ed3\u679c\u53ef\u63d0\u793a\u662f\u5426\u8fdb\u884c\u7279\u5b9aMMR\u57fa\u56e0\u7684\u7a81\u53d8\u68c0\u6d4b\u3002<\/p>\n
4MSI\u7684\u4e34\u5e8a\u610f\u4e49<\/p>\n
MSI\u6700\u65e9\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u53d1\u73b0\uff0c\u5176\u5728\u7ed3\u76f4\u80a0\u764c\u3001\u80c3\u764c\u548c\u5b50\u5bab\u5185\u819c\u764c\u7b49\u591a\u79cd\u5b9e\u4f53\u7624\u4e2d\u9ad8\u53d1,\u5728\u6797\u5947\u7efc\u5408\u5f81\u7b5b\u67e5\u3001\u5316\u7597\u836f\u7269\u9009\u62e9\u3001\u9884\u540e\u9884\u6d4b\u548c\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u83b7\u76ca\u4eba\u7fa4\u7b5b\u9009\u7b49\u65b9\u9762\u5177\u6709\u91cd\u8981\u610f\u4e49\u30022021\u5e74\uff0c\u7f8e\u56fdNCCN\u6307\u5357\u63a8\u8350\u7ed3\u76f4\u80a0\u764c\u3001\u5b50\u5bab\u5185\u819c\u764c\u3001\u80c3\u764c\u548c\u5c0f\u80a0\u817a\u764c\u7684\u65b0\u786e\u8bca\u60a3\u8005\u5e38\u89c4\u68c0\u6d4bMSI,\u540c\u65f6\u4e5f\u63a8\u8350\u524d\u5217\u817a\u764c\u3001\u80f0\u817a\u764c\u7b49\u8fdb\u884cMSI\u68c0\u6d4b\u4ee5\u6307\u5bfc\u514d\u75ab\u6cbb\u7597\u3002CSCO\u7ed3\u76f4\u80a0\u764c\u8bca\u7597\u6307\u5357\u63a8\u8350\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u884cMSI\/MMR\u68c0\u6d4b\uff0c\u300a\u7ed3\u76f4\u80a0\u764c\u5206\u5b50\u68c0\u6d4b\u9ad8\u901a\u91cf\u6d4b\u5e8f\u4e2d\u56fd\u4e13\u5bb6\u5171\u8bc6\u300b(2021)\u4e5f\u5c06MSI\/MMR\u5217\u4e3a\u201c\u5fc5\u987b\u68c0\u6d4b\u7684\u751f\u7269\u5b66\u6807\u5fd7\u7269\u201d\u3002\u300a\u5b50\u5bab\u5185\u819c\u764c\u5206\u5b50\u68c0\u6d4b\u4e2d\u56fd\u4e13\u5bb6\u5171\u8bc6\u300b(2021)\u63a8\u8350\u5bf9\u5b50\u5bab\u5185\u819c\u764cMMR\/MSI\u60a3\u8005\u884c\u6797\u5947\u7efc\u5408\u5f81\u7b5b\u67e5\u3002MSI\u68c0\u6d4b\u5bf9\u7ed3\u76f4\u80a0\u764c\u548c\u5b50\u5bab\u5185\u819c\u764c\u7b49\u591a\u79cd\u5b9e\u4f53\u7624\u60a3\u8005\u7684\u6cbb\u7597\uff0c\u5747\u6709\u91cd\u8981\u7684\u4e34\u5e8a\u610f\u4e49\u3002<\/p>\n
4.1MSI\u68c0\u6d4b\u4e0e\u6797\u5947\u7efc\u5408\u5f81\u7684\u5173\u7cfb<\/p>\n
\u6797\u5947\u7efc\u5408\u5f81\u662f\u7531MMR\u57fa\u56e0\uff08\u5305\u62ecMLH1\u3001MSH2\u3001MSH6\u548cPMS2\u57fa\u56e0\uff09\u80da\u7cfb\u81f4\u75c5\u6027\u7a81\u53d8\uff0c\u6216EPCAM\u57fa\u56e0\u5931\u6d3b\u5bfc\u81f4MSH2\u542f\u52a8\u5b50\u9ad8\u5ea6\u7532\u57fa\u5316\uff0c\u5f15\u8d77MSH2\u57fa\u56e0\u6c89\u9ed8\u6240\u81f4\u7684\u5e38\u67d3\u8272\u4f53\u663e\u6027\u9057\u4f20\u6027\u80bf\u7624\u7efc\u5408\u5f81\u3002\u6797\u5947\u7efc\u5408\u5f81\u53d1\u75c5\u65f6\u95f4\u65e9\uff0c\u7ea6\u5360\u7ed3\u76f4\u80a0\u764c\u53d1\u751f\u7387\u76843%,\u5305\u62ec\u7ed3\u76f4\u80a0\u764c\u3001\u5b50\u5bab\u5185\u819c\u764c\u3001\u5375\u5de2\u764c\u548c\u80c3\u764c\u7b49\u591a\u79cd\u80bf\u7624\u3002\u7531\u4e8eMMR\u57fa\u56e0\u7684\u529f\u80fd\u5931\u6d3b\uff0c\u5fae\u536b\u661f\u51fa\u73b0\u7684\u590d\u5236\u9519\u8bef\u5f97\u4e0d\u5230\u7ea0\u6b63\u5e76\u4e0d\u65ad\u7d2f\u79ef\uff0c90%\u7684\u6797\u5947\u7efc\u5408\u5f81\u60a3\u8005\u8868\u73b0\u4e3adMMR\u548c\uff08\u6216\uff09MSI-H\u8868\u578b\u3002\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u65e0\u8bba\u5e74\u9f84\u548c\u5206\u671f\uff0c\u884c\u6797\u5947\u7efc\u5408\u5f81\u7b5b\u67e5\u5747\u6709\u52a9\u4e8e\u53d1\u73b0\u75be\u75c5\u3002\u300a\u9057\u4f20\u6027\u7ed3\u76f4\u80a0\u764c\u4e34\u5e8a\u8bca\u6cbb\u548c\u5bb6\u7cfb\u7ba1\u7406\u4e2d\u56fd\u4e13\u5bb6\u5171\u8bc6\u300b\u63a8\u8350\u5bf9MSI-H\/dMMR\u7684\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u884cMMR\u80da\u7cfb\u68c0\u6d4b\uff0c\u4ee5\u660e\u786e\u8bca\u65ad\u6797\u5947\u7efc\u5408\u5f81\u3002<\/p>\n
4.2MSI\u68c0\u6d4b\u4e0e5-FU\u7c7b\u5316\u7597\u836f\u7269\u7684\u9009\u62e9<\/p>\n
MSI\u68c0\u6d4b\u80fd\u591f\u9884\u6d4b\u7ed3\u76f4\u80a0\u764c\u8f85\u52a9\u5316\u7597\u7684\u7597\u6548\uff0c2003\u5e74\u4e00\u9879\u56de\u987e\u6027\u7814\u7a76\u8868\u660e\uff0cMSI-H\u7ed3\u76f4\u80a0\u764c\u2161\/\u2162\u671f\u60a3\u8005\u672a\u4ece5-FU\u7684\u5355\u836f\u8f85\u52a9\u6cbb\u7597\u4e2d\u83b7\u76ca\u30022010\u5e74\uff0cSargent\u7b49\u7814\u7a76\u8bc1\u5b9e\u2161\u671fMSI-H\u7684\u7ed3\u80a0\u764c\u60a3\u8005\u672f\u540e\u9884\u540e\u8f83\u597d\uff0c\u60a3\u8005\u672a\u4ece5-FU\u5355\u836f\u5316\u7597\u4e2d\u83b7\u76ca\uff0c\u603b\u751f\u5b58\u671f(overall survival,OS)\u7f29\u77ed(HR=2.95)\u3002\u56fd\u5185\u5916\u6743\u5a01\u6307\u5357\u5747\u6307\u51fa\uff0c\u2161\u671fMSI-H\/dMMR\u7684\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u9884\u540e\u8f83\u597d\uff0c\u4e0d\u5efa\u8bae\u4f7f\u7528\u6c1f\u5c3f\u5627\u5576\u7c7b\u836f\u7269\u6cbb\u7597\u3002\u56e0\u6b64\uff0c\u2161\u671f\u60a3\u8005\u672f\u540e\u5e94\u5e38\u89c4\u884cMSI\u68c0\u6d4b\u4ee5\u5236\u5b9a\u4e2a\u4f53\u5316\u6cbb\u7597\u65b9\u6848\uff0cMSI-H\u7684\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u5e94\u5c3d\u53ef\u80fd\u907f\u514d\u6c1f\u5c3f\u5627\u5576\u7684\u5355\u836f\u8f85\u52a9\u6cbb\u7597\u3002<\/p>\n
4.3MSI\u68c0\u6d4b\u4e0e\u9884\u540e\u5206\u5c42\u5173\u7cfb<\/p>\n
MSI\u68c0\u6d4b\u5bf9\u9884\u6d4b\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u9884\u540e\u5177\u6709\u91cd\u8981\u4ef7\u503c\uff0cMSI-H\u7684\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u6709\u663e\u8457\u7684\u75c5\u7406\u7279\u5f81\uff0c\u5305\u62ec\u8fd1\u7aef\u7ed3\u80a0\u4f18\u52bf\u3001\u5206\u5316\u7a0b\u5ea6\u5dee\u3001\u4e30\u5bcc\u7684\u9ecf\u6db2\u6210\u5206\u548c\u6dcb\u5df4\u7ec6\u80de\u6d78\u6da6\u589e\u52a0\u3002MSI-H\u5728\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u53d1\u751f\u7387\u4e3a15%,\u73b0\u6709\u6570\u636e\u8868\u660e\uff0cMSI-H\/dMMR\u662f\u2161\u671f\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u7684\u72ec\u7acb\u9884\u540e\u6307\u6807\uff0c\u4e0eMSI-L\/pMMR\u60a3\u8005\u76f8\u6bd4\uff0c\u5176OS\u957f\u548c\u590d\u53d1\u98ce\u9669\u4f4e\u3002\u6b64\u5916\uff0cMSI\u8fd8\u53ef\u4f5c\u4e3a\u80c3\u764c\u548c\u5c0f\u80a0\u817a\u764c\u7684\u9884\u540e\u56e0\u5b50\u3002\u4e00\u9879\u835f\u8403\u5206\u6790\u8868\u660e\uff0cMSI-H\u80c3\u764c\u60a3\u8005\u9884\u540e\u8f83\u597d(HR=0.63),\u4f46MSI-H\u80c3\u764c\u60a3\u8005\u672a\u4ece5-FU\u5355\u836f\u8f85\u52a9\u5316\u7597\u83b7\u76ca\u3002\u5728\u5c0f\u80a0\u817a\u764c\u4e2d\uff0c\u4e0eMSS\u60a3\u8005\u76f8\u6bd4\uff0cMSI-H\u60a3\u8005\u9884\u540e\u66f4\u4f73\u3002<\/p>\n
4.4MSI\u68c0\u6d4b\u4e0e\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u83b7\u76ca\u4eba\u7fa4\u7684\u5173\u7cfb<\/p>\n
2017\u5e74\uff0c\u7f8e\u56fdFDA\u6279\u51c6PD-1\u6297\u4f53\u5e15\u535a\u5229\u73e0\u5355\u6297\uff0c\u7528\u4e8e\u4e0d\u80fd\u624b\u672f\u6216\u8f6c\u79fb\u7684MSI-H\/dMMR\u5b9e\u4f53\u7624\u60a3\u8005\u7684\u6cbb\u7597\uff0c\u5df2\u6210\u4e3a\u9996\u4e2a\u4e0d\u9650\u764c\u79cd\u3001\u4ec5\u4ee5\u751f\u7269\u5b66\u6807\u5fd7\u7269\u8fdb\u884c\u6cbb\u7597\u9009\u62e9\u7684\u6297\u80bf\u7624\u836f\u7269\u3002\u968f\u540e\uff0cCheck Mate142\u7814\u7a76\u8868\u660e,\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597MSI-H\/dMMR\u8f6c\u79fb\u6027\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u7684\u6709\u6548\u7387\u4e3a31%,\u4e2d\u4f4d\u65e0\u8fdb\u5c55\u751f\u5b58\u671f(progression-free survival,PFS)\u4e3a14.3\u4e2a\u6708\u3002\u7f8e\u56fdFDA\u6279\u51c6\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597MSI-H\u665a\u671f\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u3002KEYNOTE-177\u7814\u7a76\u8868\u660e\uff0cMSI-H\/dMMR\u60a3\u8005\u59d1\u606f\u4e00\u7ebf\u5e94\u7528\u5e15\u535a\u5229\u73e0\u5355\u6297\u3001\u6807\u51c6\u5316\u7597\u9776\u5411\u6cbb\u7597\u7684\u5ba2\u89c2\u6709\u6548\u7387(objective response rate,ORR)\u5206\u522b\u4e3a43.8%\u548c33.1%,\u4e2d\u4f4dPFS\u5206\u522b\u4e3a16.5\u548c8.2\u4e2a\u6708\uff0c\u5dee\u5f02\u6709\u7edf\u8ba1\u5b66\u610f\u4e49,\u665a\u671f\u7ed3\u76f4\u80a0\u764c\u4e00\u7ebf\u7528\u836f\u2014\u5e15\u535a\u5229\u73e0\u5355\u6297\u4e5f\u518d\u6b21\u83b7\u6279\uff0cMSI\u8dfb\u8eab\u4e3a\u4e00\u7ebf\u6cbb\u7597\u6807\u5fd7\u7269\u30022021\u5e74\uff0c\u6211\u56fd\u9996\u6b3e\u81ea\u4e3b\u7814\u53d1\u7684PD-L1\u6297\u4f53\u6069\u6c83\u5229\u5355\u6297\u7ecf\u56fd\u5bb6\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40(National Medical Products Administration,NMPA)\u83b7\u6279\u4e0a\u5e02\uff0c\u7528\u4e8eMSI-H\/dMMR\u6210\u4eba\u665a\u671f\u5b9e\u4f53\u7624\u60a3\u8005\u6cbb\u7597\uff0c\u7ed3\u76f4\u80a0\u764c\u3001\u80c3\u764c\u548c\u5176\u4ed6\u5b9e\u4f53\u7624\u60a3\u8005\u7684ORR\u4e3a42.7%,\u75be\u75c5\u63a7\u5236\u7387\u4e3a66.0%,\u6297\u80bf\u7624\u7597\u6548\u4f73\uff0c\u4e3a\u60a3\u8005\u589e\u52a0\u65b0\u7684\u6cbb\u7597\u9009\u62e9\u3002\u603b\u4e4b\uff0cMSI-H\/dMMR\u665a\u671f\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u53ef\u4ecePD-1\/PD-L1\u6cbb\u7597\u4e2d\u83b7\u76ca\uff0c\u901a\u8fc7\u68c0\u6d4bMSI\u72b6\u6001\u53ef\u4ee5\u9884\u4f30\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u7684\u4f7f\u7528\u4ef7\u503c\u3002<\/p>\n
5MSI\u7684\u68c0\u6d4b\u65b9\u6cd5<\/p>\n
5.1PCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6280\u672f<\/p>\n
\u91c7\u7528\u591a\u91cd\u8367\u5149\u805a\u5408\u9176\u94fe\u5f0f\u53cd\u5e94\u6269\u589e(quantitive fluorescent polymerasechain reaction,QFPCR)\u7ed3\u5408\u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6cd5\uff0c\u5bf9\u5fae\u536b\u661f\u4f4d\u70b9\u548c\u5bf9\u7167\u4f4d\u70b9\u8fdb\u884c\u68c0\u6d4b\u3002\u5f53\u5fae\u536b\u661f\u4f4d\u70b9\u7528\u4e8e\u5224\u5b9a\u6837\u672cMSI\u72b6\u6001\uff0c\u5bf9\u7167\u4f4d\u70b9\u9664\u4f5c\u4e3a\u5185\u90e8\u8d28\u63a7\u5916\uff0c\u8fd8\u53ef\u7528\u4e8e\u9a8c\u8bc1\u80bf\u7624\u7ec4\u7ec7\u548c\u6b63\u5e38\u7ec4\u7ec7\u662f\u5426\u6765\u81ea\u540c\u4e00\u4e2a\u4f53\u3002\u6269\u589e\u4f53\u7cfb\u4e2d\u5bf9\u6bcf\u4e2a\u68c0\u6d4b\u4f4d\u70b9\u8bbe\u7f6e2\u6761\u5f15\u7269\uff0c\u5176\u4e2d1\u6761\u6807\u8bb0\u7279\u5b9a\u8367\u5149\u57fa\u56e2\u3002\u5f15\u7269\u4e0e\u5bf9\u5e94\u7684\u57fa\u56e0\u7ec4DNA\u6a21\u677f\u7ed3\u5408\u8fdb\u884c\u6269\u589e\uff0c\u4ea7\u751f\u7279\u5b9a\u957f\u5ea6\u548c\u8367\u5149\u6807\u8bb0\u7684\u6269\u589e\u4ea7\u7269\uff0c\u6269\u589e\u4ea7\u7269\u7528\u6bdb\u7ec6\u7ba1\u7535\u6cf3\u68c0\u6d4b\uff0c\u901a\u8fc7\u7279\u5b9a\u957f\u5ea6\u7684\u4ea7\u7269\u53ef\u4ee5\u5224\u5b9a\u7279\u5b9a\u4f4d\u70b9\u91cd\u590d\u5355\u5143\u7684\u91cd\u590d\u72b6\u6001\u3002<\/p>\n
\u76ee\u524d\uff0cPCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6280\u672f\u662fMSI\u68c0\u6d4b\u7684\u516c\u8ba4\u201c\u91d1\u6807\u51c6\u201d\u3002\u9996\u5148\u68c0\u6d4b\u65f6\u5206\u522b\u63d0\u53d6\u80bf\u7624\u6837\u672c\u548c\u5bf9\u7167\u6837\u672c\u7684DNA,\u5176\u6b21\u4f7f\u7528\u8bd5\u5242\u76d2\u5bf9\u6b63\u5e38\u7ec4\u7ec7\u548c\u80bf\u7624\u7ec4\u7ec7\u7684DNA\u8fdb\u884cPCR\u6269\u589e\uff0c\u91c7\u7528\u57fa\u56e0\u5206\u6790\u4eea\u8fdb\u884cDNA\u7247\u6bb5\u5206\u6790\uff0c\u6bd4\u8f83\u80bf\u7624\u7ec4\u7ec7\u548c\u5bf9\u7167\u7ec4\u7ec7\u4e2d\u5404\u5fae\u536b\u661f\u4f4d\u70b9\u7684\u7535\u6cf3\u56fe\u5cf0\u578b\u548c\u6570\u76ee\uff0c\u5224\u65ad\u80bf\u7624\u7ec4\u7ec7\u76f8\u5e94\u4f4d\u70b9\u7684\u4e0d\u7a33\u5b9a\u72b6\u6001\u3002<\/p>\n
\u4e3a\u907f\u514dPCR\u5b9e\u9a8c\u5ba4\u6c61\u67d3\uff0c\u5efa\u8bae\u9009\u7528\u542b\u6709\u5c3f\u5627\u5576DNA\u7cd6\u57fa\u5316\u9176(UDG)\u9632\u6c61\u67d3MSI\u68c0\u6d4b\u4f53\u7cfb,\u5728PCR\u6269\u589e\u524d\u6d88\u5316\u53ef\u80fd\u5b58\u5728\u542b\u6709\u5c3f\u5627\u5576\u7684\u6269\u589e\u4ea7\u7269\uff0c\u4fdd\u8bc1\u5b9e\u9a8c\u7ed3\u679c\u7684\u51c6\u786e\u6027\u3002<\/p>\n
5.1.1\u4f4d\u70b9\u9009\u62e9<\/p>\n
\u76ee\u524d\uff0c\u672c\u6587\u63a8\u8350\u9009\u7528\u5df2\u901a\u8fc7NMPA\u6216FDA\u6ce8\u518c\u5ba1\u6279\u8981\u6c42\u7684\u8bd5\u5242\u76d2\u4f4d\u70b9\u7ec4\u5408\uff0c\u5982\uff1a(1)BAT-25\u3001BAT-26\u3001D2S123\u3001D17S250\u548cD5S346;(2)BAT-25\u3001BAT-26\u3001NR-21\u3001NR24\u3001MONO-27\u548cNR-27;(3)BAT-25\u3001BAT-26\u3001NR-21\u3001NR-24\u548cMONO-27\u3002\u540c\u65f6\u4e3a\u4fdd\u8bc1\u7ed3\u679c\u7684\u51c6\u786e\u6027\uff0c\u53ef\u589e\u52a0\u5bf9\u7167\u4f4d\u70b9\u4f5c\u4e3a\u5185\u90e8\u8d28\u63a7\uff0c\u5e38\u89c1\u5bf9\u7167\u4f4d\u70b9\u4e3aPentaC\u3001PentaD\u548cAmel\u7b49\u3002<\/p>\n
5.1.2\u68c0\u6d4b\u6d41\u7a0b<\/p>\n
\u68c0\u6d4b\u6d41\u7a0b\u5305\u62ec\uff1aDNA\u63d0\u53d6\u3001PCR\u6269\u589e\u3001\u6bdb\u7ec6\u7ba1\u7535\u6cf3\u5206\u79bb\u6837\u54c1\u548c\u7ed3\u679c\u5206\u6790\u3002<\/p>\n
5.2PCR \u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5<\/p>\n
\u9664\u591a\u91cd\u8367\u5149PCR\u7ed3\u5408\u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6cd5\u5916\uff0c\u4e5f\u53ef\u4f7f\u7528PCR\u7ed3\u5408\u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u68c0\u6d4b\u76f8\u5173MSI\u6807\u5fd7\u7269\u3002\u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u901a\u8fc7\u5728\u53cd\u5e94\u4f53\u7cfb\u4e2d\u52a0\u5165\u9971\u548cDNA\u53cc\u94fe\u8367\u5149\u67d3\u6599\uff0cPCR\u7ed3\u675f\u540e\u8fdb\u884cDNA\u53cc\u94fe\u4ea7\u7269\u5347\u6e29\u89e3\u94fe\u53cd\u5e94\u83b7\u53d6\u8367\u5149\u4fe1\u53f7\u3002\u968f\u7740\u6e29\u5ea6\u5347\u9ad8\uff0cDNA\u53cc\u94fe\u6c22\u952e\u4e0d\u65ad\u88ab\u6253\u5f00\uff0c\u8367\u5149\u67d3\u6599\u91ca\u653e\uff0c\u8367\u5149\u5f3a\u5ea6\u9010\u6e10\u964d\u4f4e\u3002\u4e0d\u540c\u6838\u9178\u7247\u6bb5\u6709\u7279\u5f02\u6027\u6e29\u5ea6\uff0c\u5373\u8367\u5149\u5f3a\u5ea6\u53d8\u5316\u66f2\u7ebf\uff08\u53c8\u79f0\u7194\u89e3\u66f2\u7ebf\uff09\u3002\u603b\u7684DNA\u53cc\u87ba\u65cb\u7ed3\u6784\u964d\u89e3\u4e00\u534a\u7684\u6e29\u5ea6\u79f0\u4e3a\u7194\u89e3\u6e29\u5ea6(Tm),\u4e0d\u540c\u5e8f\u5217DNA\u7684Tm\u503c\u4e0d\u540c\u3002DNA\u4e2dG-C\u542b\u91cf\u4e0eTm\u503c\u6210\u6b63\u6bd4\uff0cG-C\u542b\u91cf\u8d8a\u9ad8\uff0cTm\u503c\u8d8a\u9ad8\u3002\u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u901a\u8fc7\u6bd4\u8f83\u4e0d\u540c\u6837\u672c\u4e4b\u95f4\u7194\u89e3\u66f2\u7ebf\u7684\u4f4d\u7f6e\u548c\u5f62\u72b6\u4e0a\u7684\u5dee\u5f02\uff0c\u533a\u5206\u57fa\u56e0\u7684\u5206\u578b\u3002<\/p>\n
\u7194\u89e3\u66f2\u7ebf\u6280\u672f\u88ab\u8ba4\u4e3a\u662f\u6700\u9002\u5408\u5206\u8fa8\u5355\u78b1\u57fa\u7684\u5dee\u5f02\uff0c\u56e0\u4e3a\u9971\u548c\u67d3\u6599\u7684\u4f7f\u7528\uff0c\u663e\u8457\u63d0\u9ad8\u4e86\u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u5728\u5355\u78b1\u57fa\u7a81\u53d8\u3001\u5c0f\u7247\u6bb5\u63d2\u5165\uff0f\u7f3a\u5931\u65b9\u9762\u68c0\u6d4b\u7684\u7075\u654f\u5ea6\u548c\u5206\u8fa8\u7387\u3002PCR\u7ed3\u5408\u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u68c0\u6d4b\u76f8\u5173MSI\u5355\u6001\u6027\u751f\u7269\u5b66\u6807\u5fd7\u7269\uff0c\u8be5\u6807\u5fd7\u7269\u4e00\u822c\u4e3a8~12\u4e2aA\u6216T\u78b1\u57fa\u7684\u5355\u78b1\u57fa\u91cd\u590d\u5e8f\u5217\uff08\u5747\u805a\u7269\uff09\uff0c\u5206\u5e03\u5728\u591a\u4e2a\u57fa\u56e0\u4e2d\u3002\u5728\u6b63\u5e38\u7ec6\u80de\uff08\u5373MMR\u529f\u80fd\u6b63\u5e38\u7684\u7ec6\u80de\uff09\u4e2d\u78b1\u57fa\u6570\u76ee\u4fdd\u6301\u7a33\u5b9a\uff08\u598211\u4e2a\uff09\u3002\u5728MMR\u529f\u80fd\u7f3a\u9677\u7684\u7ec6\u80de\uff08\u5982\u764c\u7ec6\u80de\uff09\u4e2d\uff0c\u8fd9\u4e9b\u5747\u805a\u7269\u66f4\u6613\u53d8\uff0c\u5e76\u4e14\u901a\u5e38\u89c2\u5bdf\u52301\u62162\u4e2a\u78b1\u57fa\u5bf9\u7684\u5220\u9664\uff0c\u5c06\u957f\u5ea6\u4e3a11\u7684\u5747\u805a\u7269\u4e0e\u957f\u5ea6\u4e3a10\u7684\u5747\u805a\u7269\u7528\u4e8e\u9274\u522bMMR\u7684\u7f3a\u9677\u3002<\/p>\n
5.2.1\u4f4d\u70b9\u9009\u62e9<\/p>\n
Zhao\u7b49\u5bf9MMR\u7f3a\u9677\u7684\u80bf\u7624\u884c\u5168\u57fa\u56e0\u7ec4\u6d4b\u5e8f(whole genome sequencing,WGS)\u5206\u6790\uff0c\u53d1\u73b059\u4e2a\u5355\u6838\u82f7\u9178\u5fae\u536b\u661f\u4f4d\u70b9\u5bf9MSI\u68c0\u6d4b\u5177\u6709\u4ee3\u8868\u610f\u4e49\uff0c\u5176\u4e2d50\u4e2a\u4f4d\u70b9\u4f4d\u4e8e\u975e\u7ffb\u8bd1\u533a\uff0c\u63d0\u793a\u7ec4\u7ec7\u7279\u5f02\u6027\u597d\u300259\u4e2a\u5747\u805a\u7269\u957f\u5ea6\u226412bp,\u4e0ePCR\u6280\u672f\u548cNGS\u6280\u672f\u90fd\u80fd\u8f83\u597d\u5730\u517c\u5bb9\u3002<\/p>\n
\u76ee\u524d\uff0c\u67092\u7ec4\u8f83\u4e3a\u6210\u719f\u7684\u6807\u5fd7\u7269\u7ec4\u5408\uff1a(1)ACVR2A\u3001BT-BD7\u3001DIDO1\u3001MRE11\u3001RYR3\u3001SEC31A\u548cSULF2;(2)EIF4E3\u3001IFT140\u3001PPP1CC\u3001UBAC2\u3001PRR5-ARHGAP8\u3001ACVR2A\u3001TAOK3\u548cRBM14-RBM4\u3002<\/p>\n
5.2.2\u68c0\u6d4b\u6d41\u7a0b<\/p>\n
\u68c0\u6d4b\u6d41\u7a0b\u5305\u62ec\uff1aDNA\u63d0\u53d6\u3001PCR\u6269\u589e\u3001\u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u68c0\u6d4b\u548c\u7ed3\u679c\u5206\u6790\u3002<\/p>\n
5.3NGS\u68c0\u6d4b<\/p>\n
MSI\u72b6\u6001\u53ef\u5e94\u7528WGS\u3001\u5168\u5916\u663e\u5b50\u7ec4\u6d4b\u5e8f(whole exon sequencing,WES)\u6216\u9776\u5411\u6d4b\u5e8f(targeted gene sequencing,TGS)\u7b49NGS\u6280\u672f\u8fdb\u884c\u68c0\u6d4b\u3002\u7f8e\u56fdNCCN\u7ed3\u76f4\u80a0\u764c\u4e34\u5e8a\u5b9e\u8df5\u6307\u5357(2022)\u63a8\u8350\u53ef\u4f7f\u7528\u7ecf\u9a8c\u8bc1\u7684NGS Panel\u8fdb\u884cMSI\u68c0\u6d4b\uff0c\u5c24\u5176\u9002\u7528\u4e8e\u9700RAS\u548cBRAF\u57fa\u56e0\u5206\u578b\u7684\u8f6c\u79fb\u6027\u7ed3\u76f4\u80a0\u764c\u60a3\u8005;\u7f8e\u56fdNCCN\u5c0f\u80a0\u817a\u764c\u4e34\u5e8a\u5b9e\u8df5\u6307\u5357(2023)\u4e2dMSI\u68c0\u6d4b\u4ec5\u63a8\u8350\u7ecf\u9a8c\u8bc1\u7684NGS Panel\u3002\u300a\u7ed3\u76f4\u80a0\u764c\u53ca\u5176\u4ed6\u76f8\u5173\u5b9e\u4f53\u7624\u5fae\u536b\u661f\u4e0d\u7a33\u5b9a\u6027\u68c0\u6d4b\u4e2d\u56fd\u4e13\u5bb6\u5171\u8bc6\u300b(2019)\u3001\u300a\u7ed3\u76f4\u80a0\u764c\u9776\u5411\u6cbb\u7597\u4e2d\u56fd\u4e13\u5bb6\u5171\u8bc6\u300b(2022)\u548c\u300a\u4e2d\u56fd\u7ed3\u76f4\u80a0\u764c\u809d\u8f6c\u79fb\u8bca\u65ad\u548c\u7efc\u5408\u6cbb\u7597\u6307\u5357\u300b(2023),\u4ea6\u63a8\u8350\u53ef\u901a\u8fc7\u7ecf\u9a8c\u8bc1\u7684NGS\u6cd5\u8fdb\u884cMSI\u68c0\u6d4b\u3002NGS\u68c0\u6d4bMSI\u7684\u4f18\u52bf\uff1a\u53ef\u8986\u76d6\u5927\u91cf\u7684\u5fae\u536b\u661f\u4f4d\u70b9\uff0c\u6839\u636ePanel\u8bbe\u8ba1\u4e0d\u540c\uff0c\u53ef\u68c0\u6d4b\u4e94\u81f3\u6570\u5341\u4e07\u4e2a\u7684\u5fae\u536b\u661f\u4f4d\u70b9\uff0c\u53ef\u9488\u5bf9\u7279\u5f02\u6027\u80bf\u7624\u6216\u6cdb\u80bf\u7624\u9009\u62e9\u4e0d\u540c\u7684\u4f4d\u70b9\u7ec4\u5408\uff0c\u5bf9MSI\u72b6\u6001\u7684\u8bc4\u4f30\u66f4\u52a0\u5168\u9762\u3002<\/p>\n
\u76ee\u524d\uff0cNGS\u5f00\u53d1\u7684Panel\u4e3b\u8981\u6839\u636e\u4e24\u79cd\u68c0\u6d4b\u539f\u7406\uff0c\u901a\u8fc7\u4e0d\u540c\u7684\u7b97\u6cd5\u6765\u68c0\u6d4bMSI\u3002(1)\u901a\u8fc7\u6bd4\u8f83\u80bf\u7624\u6837\u672c\u4e0e\u6b63\u5e38\u5bf9\u7167\u6837\u672c\uff08\u6216\u6b63\u5e38\u4eba\u7684\u57fa\u7ebf\u6c34\u5e73\uff09\u4e4b\u95f4\u7684\u5fae\u536b\u661f\u91cd\u590d\u5e8f\u5217\u957f\u5ea6\u5206\u5e03\uff0c\u4ee5\u4e0d\u7a33\u5b9a\u4f4d\u70b9\u6bd4\u4f8b\u662f\u5426\u8d85\u8fc7\u65e2\u5b9a\u9608\u503c\u6765\u5224\u65ad\u5fae\u536b\u661f\u72b6\u6001\u3002\u5982MSI-sensor\u4f7f\u7528\u6210\u5bf9\u7684\u80bf\u7624\u548c\u6b63\u5e38WES\u6570\u636e\uff0c\u6bd4\u8f83\u5355\u6838\u82f7\u9178\u5230\u4e94\u6838\u82f7\u9178\u91cd\u590d\u5fae\u536b\u661f\u7684\u7b49\u4f4d\u57fa\u56e0\u957f\u5ea6\u5206\u5e03\uff0c\u5e76\u5bf9\u6bcf\u4e2a\u5206\u6790\u7684\u57fa\u56e0\u5ea7\u5e94\u7528\u03c72\u5206\u6790\uff0c\u7ed9\u51fa\u5bf9\u5e94\u4e8e\u4e0d\u7a33\u5b9a\u5fae\u536b\u661f\u57fa\u56e0\u5ea7\u767e\u5206\u6bd4\u7684MSI\u5f97\u5206\uff0c\u9608\u503c\u4e3a3.5%\u3002MSI-Colon Core\u4e2d\u5fae\u536b\u661f\u72b6\u6001\u7531\u6837\u672c\u4e2d\u4e0d\u7a33\u5b9a\u57fa\u56e0\u5ea7\u4e0e\u6b63\u5e38\u57fa\u7ebf\u6c34\u5e73\u7684\u767e\u5206\u6bd4\u6765\u786e\u5b9a\uff0c\u9608\u503c\u4e3a40%\u3002(2)\u57fa\u4e8e\u5e8f\u5217\u4e2d\u7684\u7a81\u53d8\u8d1f\u8377\u548c\uff08\u6216\uff09\u5fae\u536b\u661f\u4e2d\u7684\u7a81\u53d8\u8d1f\u8377\u5224\u65adMSI\u72b6\u6001\uff0c\u5982MSI-seq Index\u662f\u57fa\u4e8eRNA\u6d4b\u5e8f\u6570\u636e\u548c\u4e24\u4e2a\u6d4b\u91cf\u503c(PI-\u5fae\u536b\u661f\u4e2d\u7684\u63d2\u5165\u5360RNA\u8f6c\u5f55\u672c\u4e2d\u6240\u6709\u63d2\u5165\u7684\u6bd4\u4f8b\uff1bPD-\u5fae\u536b\u661f\u4e2d\u7684\u7f3a\u5931\u5360RNA\u8f6c\u5f55\u672c\u4e2d\u6240\u6709\u7f3a\u5931\u7684\u6bd4\u4f8b\uff09\u7684\u6bd4\u7387\u68c0\u6d4bMSI\u72b6\u6001\uff0cMSI-H\u7684PI\/PD\u6bd4\u503c<0.9\u3002Nowak\u7b49\u4f7f\u7528275\u4e2a\u4e0e\u764c\u75c7\u76f8\u5173\u7684\u57fa\u56e0\u5b9a\u5411\u6d4b\u5e8f\u6570\u636e\uff0c\u628a\u603b\u7a81\u53d8\u8d1f\u62c5(>40Mb)\u548c\u5355\u6838\u82f7\u9178\u5fae\u536b\u661f\u4e2d\u7684INDELs(>5Mb)\u5b9a\u4e49\u4e3aMSI-H\u3002NGS\u5e73\u53f0\u7684MSI\u7b97\u6cd5\u5305\u62ec\u4f46\u4e0d\u9650\u4e8eMSI-sensor\u3001MSI-ColonCore\u3001MSI-seqIndex\u548cNowak\u7b49\uff0c\u968f\u7740NGS\u7684\u4e0d\u65ad\u53d1\u5c55\uff0c\u5c06\u9646\u7eed\u5f00\u53d1\u51fa\u66f4\u591a\u65b0\u7b97\u6cd5\uff0c\u4e0d\u65ad\u63d0\u9ad8NGS\u68c0\u6d4bMSI\u7684\u51c6\u786e\u5ea6\u548c\u654f\u611f\u5ea6\u3002<\/p>\n
\u4e34\u5e8a\u548c\u75c5\u7406\u533b\u5e08\u5bf9\u65e0\u6cd5\u83b7\u53d6\u80bf\u7624\u7ec4\u7ec7\u7684\u60a3\u8005\uff0c\u53ef\u4f7f\u7528\u5916\u5468\u8840\u5faa\u73af\u80bf\u7624DNA(circulating tumorDNA,ctDNA)\u8fdb\u884cMSINGS\u68c0\u6d4b\u7531\u4e8e\u6db2\u4f53\u6d3b\u68c0\u8bca\u65ad\u7684\u51c6\u786e\u6027\u548c\u7075\u654f\u5ea6\u6709\u9650\uff0c\u76ee\u524d\u4e0d\u63a8\u8350\u5e38\u89c4\u884cctDNA\u7684MSINGS\u68c0\u6d4b\uff0c\u4ec5\u4f5c\u4e3a\u65e0\u6cd5\u83b7\u53d6\u80bf\u7624\u60a3\u8005\u8bc4\u4ef7MSI\u72b6\u6001\u7684\u66ff\u4ee3\u68c0\u6d4b\u3002<\/p>\n
6\u68c0\u6d4b\u7684\u6837\u672c\u7c7b\u578b\u4e0e\u8981\u6c42<\/p>\n
6.1\u80bf\u7624\u6d3b\u68c0\u6216\u624b\u672f\u7684\u65b0\u9c9c\u6807\u672c<\/p>\n
\u5efa\u8bae\u6807\u672c\u79bb\u4f53\u540e30min\u5185\uff0c\u7f6e\u4e8e\u6db2\u6c2e\u6216-80\u2103\u4fdd\u5b58\uff0c\u9632\u6b62\u6838\u9178\u964d\u89e3\u3002<\/p>\n
6.2\u798f\u5c14\u9a6c\u6797\u56fa\u5b9a\u77f3\u8721\u5305\u57cb\u6807\u672c<\/p>\n
\u5efa\u8bae\u6807\u672c\u79bb\u4f53\u540e30min\u5185\uff0c\u7ecf10%\u4e2d\u6027\u798f\u5c14\u9a6c\u6797\u5145\u5206\u56fa\u5b9a\uff0c\u6d3b\u68c0\u5c0f\u6807\u672c\u56fa\u5b9a6~12h,\u624b\u672f\u5927\u6807\u672c\u5e94\u5207\u5f00\u56fa\u5b9a6~48h\u3002\u8721\u5757\u4fdd\u5b58\u7684\u73af\u5883\u5e94\u6e29\u6e7f\u5ea6\u6052\u5b9a\uff0c\u5c3d\u91cf\u51cf\u7f13\u6838\u9178\u964d\u89e3\u3002<\/p>\n
6.3\u77f3\u8721\u5207\u7247\u6570\u91cf\u8981\u6c42<\/p>\n
\u798f\u5c14\u9a6c\u6797\u56fa\u5b9a\u77f3\u8721\u5305\u57cb\u7ec4\u7ec7\u5207\u7247\u539a5~8\u03bcm,\u5207\u7247\u6570\u91cf\u22655\u5f20\uff0c\u7ec4\u7ec7\u5927\u5c0f\u22651cm\u00d71cm\u3002PCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6280\u672f\u68c0\u6d4bMSI\u9700\u9009\u62e9\u764c\u65c1\u7ec4\u7ec7\u6216\u5916\u5468\u8840\u4f5c\u4e3a\u5bf9\u7167\u6837\u672c\uff0cPCR \u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u548cNGS\u6280\u672f\u65e0\u9700\u5bf9\u7167\u6837\u672c\u3002<\/p>\n
6.4\u8840\u6db2\u6807\u672c<\/p>\n
\u6839\u636e\u4e0d\u540cPanel\u68c0\u6d4b\u8981\u6c42\u9009\u62e9\u5408\u9002\u6297\u51dd\u5242\u7684\u91c7\u8840\u7ba1\u6216\u4e13\u7528\u4fdd\u5b58\u7ba1\uff0c\u8840\u6db2\u6807\u672c\u7684\u91c7\u96c6\u3001\u8fd0\u8f93\u548c\u4fdd\u5b58\u5e94\u4e25\u683c\u6309\u7167\u76f8\u5173\u64cd\u4f5c\u6d41\u7a0b\u8fdb\u884c\uff0c\u8840\u6db2\u6807\u672c\u5e94\u5728\u91c7\u96c62h\u5185\u5b8c\u6210\u5904\u7406\uff0c\u907f\u514d\u53cd\u590d\u51bb\u878d\uff0c\u9632\u6b62\u6838\u9178\u964d\u89e3\u3002<\/p>\n
6.5\u6838\u9178\u6837\u672c\u7528\u91cf<\/p>\n
\u63d0\u53d6\u7684\u57fa\u56e0\u7ec4DNA\u53ef\u901a\u8fc7\u7d2b\u5916\u5206\u5149\u5149\u5ea6\u4eea\u6216Qubit\u7b49\u68c0\u6d4b\u6d53\u5ea6\uff0c\u5fc5\u8981\u65f6\u5bf9DNA\u6837\u672c\u8fdb\u884c\u6d53\u5ea6\u8c03\u6574\u548c\u7a00\u91ca\uff0c\u786e\u4fdd\u5355\u4e2aPCR\u7ba1\u4e2dDNA\u7684\u4e0a\u6837\u91cf\u4e3a10~250ng\u3002\u63d0\u53d6DNA\u6837\u672c\u4e8e2~8\u2103\u4fdd\u5b587\u5929\u5185\u68c0\u6d4b\uff0c\u4e8e-20\u2103\u4fdd\u5b586\u4e2a\u6708\u5185\u68c0\u6d4b\u3002<\/p>\n
\u672c\u6587\u5efa\u8bae\u4f7f\u7528Qubit\u68c0\u6d4bDNA\u6d53\u5ea6\uff0c\u7531\u4e8e\u63d0\u53d6\u7684DNA\u6837\u672c\u4e2d\u6df7\u6709\u4e0d\u540c\u6bd4\u4f8bRNA,\u7d2b\u5916\u5438\u6536\u6cd5\u53ef\u80fd\u9ad8\u4f30\u6837\u672c\u4e2dDNA\u7684\u6d53\u5ea6\uff0cQubit\u68c0\u6d4b\u52a0\u5165DNA\u67d3\u6599\u53ef\u51c6\u786e\u68c0\u6d4bDNA\u6d53\u5ea6\u3002<\/p>\n
7\u8d28\u91cf\u63a7\u5236<\/p>\n
\u6807\u672c\u7684\u8d28\u91cf\u63a7\u5236\u5728\u68c0\u6d4b\u7684\u524d\u3001\u4e2d\u3001\u540e\u5404\u8fc7\u7a0b\u4e2d\u5e94\u6ce8\u610f\u4ee5\u4e0b\u51e0\u70b9\uff1a(1)\u5f85\u6d4b\u6837\u672c\u9700\u75c5\u7406\u533b\u5e08\u8fdb\u884c\u53ef\u884c\u6027\u8bc4\u4f30\uff0c\u4e00\u822c\u80bf\u7624\u7ec6\u80de\u6bd4\u4f8b\uff1e20%,\u7ec6\u80de\u5b66\u6837\u672c\u4e2d\u80bf\u7624\u7ec6\u80de\u6570\uff1e200\u4e2a\u3002\u5fc5\u8981\u65f6\u53ef\u5b8f\u89c2\u89e3\u5256\u6216\u663e\u5fae\u5207\u5272\u5bcc\u96c6\u80bf\u7624\u7ec6\u80de\uff1b(2)\u9700\u6709\u72ec\u7acb\u7684\u5207\u7247\u8bbe\u5907\u548c\u573a\u5730\uff0c\u4f7f\u7528\u4e00\u6b21\u6027\u5200\u7247\u3001\u68c9\u7b7e\u548c\u6f02\u7247\u6db2\uff0c\u907f\u514d\u5207\u7247\u65f6\u6837\u672c\u4e4b\u95f4\u7684\u4ea4\u53c9\u6c61\u67d3\uff1b(3)PCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6cd5\u68c0\u6d4bMSI\u5206\u5b50\u91cf\u5185\u6807\u9700\u5408\u683c\uff0c\u91c7\u7528\u7ecf\u8bd5\u5242\u76d2\u914d\u5957\u9a8c\u8bc1\u7684\u5206\u5b50\u91cf\u5185\u6807\uff0c\u5404\u7247\u6bb5\u5927\u5c0f\u6807\u6ce8\u6b63\u786e\uff1b\u5982\u91c7\u7528\u5176\u4ed6\u5916\u914d\u5206\u5b50\u91cf\u5185\u6807\u5219\u9700\u8fdb\u884c\u9a8c\u8bc1\uff0c\u4fdd\u8bc1\u65e0\u660e\u663e\u8367\u5149\u6e17\u900f\u73b0\u8c61\uff1b(4)\u5fae\u536b\u661f\u4f4d\u70b9\u68c0\u6d4b\u5cf0\u9ad8\uff0c\u672a\u51fa\u73b0\u8d85\u9608\u503c(3500\/3500xl\u30013500Dx\/3500xLDx\u3001GenReader7010,\u5cf0\u9ad8<30000;3130xl,\u5cf0\u9ad8<8000);\u53cd\u4e4b\uff0c\u5e94\u8c03\u6574\u4ea7\u7269\u7a00\u91ca\u6bd4\u4f8b\u91cd\u65b0\u68c0\u6d4b\uff0c\u53ef\u53d6PCR\u4ea7\u7269\u22652\u03bcL\u7528\u7eaf\u5316\u6c34\u7a00\u91ca2~40\u500d\uff0c\u5c06\u7a00\u91ca\u540e\u7684\u4ea7\u7269\u8fdb\u884c\u6bdb\u7ec6\u7ba1\u7535\u6cf3\u5206\u79bb\uff1b(5)\u5f85\u68c0\u6d4b\u4f4d\u70b9\u548c\u5185\u53c2\u4f4d\u70b9\u5f15\u7269\u8367\u5149\u57fa\u56e2\u6807\u8bb0\u53ca\u5176\u4ea7\u7269\u7247\u6bb5\u5927\u5c0f\uff0c\u7b26\u5408\u9884\u671f\uff1b(6)\u7a7a\u767d\u5bf9\u7167\u4ee5\u65e0\u6838\u9178\u9176\u7eaf\u6c34\u4e3a\u6a21\u677f\u8fdb\u884c\u6269\u589e\uff0c\u65e0\u4efb\u4f55\u6269\u589e\u4ea7\u7269\uff1b(7)\u4ee5\u8d28\u63a7\u54c1\u4e3a\u6a21\u677f\u8fdb\u884c\u6269\u589e\uff0c\u6240\u6709\u8d28\u63a7\u5185\u53c2\u4f4d\u70b9\u6709\u6548\u5cf0\u4f4d\u7f6e\u4e0e\u9884\u671f\u76f8\u5dee<2nt;(8)\u6bcf\u4e2a\u5bf9\u7167\u4f4d\u70b9\u81f3\u5c11\u51fa\u73b01\u4e2a\u4e0d\u4f4e\u4e8e100RFU\u7684\u4ea7\u7269\u5cf0\uff0c\u6838\u5b9e\u540c\u4e00\u7ec4\u80bf\u7624\u6837\u672c\u548c\u5bf9\u7167\u6837\u672c\u7684\u5bf9\u7167\u4f4d\u70b9\u662f\u5426\u4e00\u81f4\uff1b\u6bcf\u4e2a\u5fae\u536b\u661f\u4f4d\u70b9\u81f3\u5c11\u51fa\u73b0\u4e00\u7ec4\u8fde\u7eed\u5cf0\uff0c\u5176\u6700\u9ad8\u5cf0\u2265100RFU;(9)\u91c7\u7528NGS\u68c0\u6d4bMSI\u7684Panel,\u5e94\u505a\u597d\u5b9e\u9a8c\u64cd\u4f5c\u548c\u751f\u7269\u4fe1\u606f\u7b49\u4fe1\u606f\u786e\u8ba4\uff1b(10)\u6587\u5e93\u7684\u8d28\u91cf\u662f\u5f71\u54cdNGS\u6570\u636e\u7684\u5173\u952e\uff0c\u5efa\u8bae\u4f7f\u7528\u8367\u5149\u5b9a\u91cf\u6216\u5176\u4ed6\u51c6\u786e\u6027\u9ad8\u7684\u65b9\u6cd5\u9274\u5b9a\uff0c\u5b9e\u9a8c\u4e2d\u9700\u8bbe\u7f6e\u9634\u9633\u6027\u76d1\u63a7\u6574\u4e2a\u5b9e\u9a8c\u6d41\u7a0b\uff1b\u6839\u636e\u6d4b\u5e8f\u6df1\u5ea6\u3001\u6d4b\u5e8f\u8986\u76d6\u5ea6\u3001\u6570\u636e\u4ea7\u51fa\u548c\u8fd0\u884c\u65f6\u95f4\u7b49\u9009\u62e9\u5408\u9002\u7684NGS\u6d4b\u5e8f\u5e73\u53f0\uff0c\u5e76\u505a\u76f8\u5e94\u6307\u6807\u7684\u8d28\u63a7\u6807\u51c6\uff1b(11)\u5b9e\u9a8c\u64cd\u4f5c\u3001\u751f\u7269\u4fe1\u606f\u5206\u6790\u548c\u62a5\u544a\u5206\u6790\u7b49\u4eba\u5458\u5e94\u53d6\u5f97\u4e0a\u5c97\u8d44\u8d28\uff0c\u53c2\u52a0\u5fc5\u8981\u7684\u57f9\u8bad\uff1b(12)\u8fdb\u884c\u6708\u5ea6\u6216\u5b63\u5ea6\u7684\u6570\u636e\u7edf\u8ba1\uff0c\u5206\u6790MSI-H\u7684\u9891\u7387\u4e0e\u6587\u732e\u62a5\u9053\u662f\u5426\u76f8\u7b26\uff1b(13)\u5b9e\u9a8c\u5ba4\u5e94\u5b9a\u671f\u53c2\u52a0\u76f8\u5e94\u7684\u5ba4\u95f4\u8d28\u8bc4\u6216\u9009\u62e9\u540c\u7ea7\u522b\u6216\u9ad8\u7ea7\u522b\u7684\u5b9e\u9a8c\u5ba4\uff0c\u8fdb\u884c\u5ba4\u95f4\u6bd4\u5bf9\u3002<\/p>\n
8\u7ed3\u679c\u5224\u8bfb\u548c\u62a5\u544a\u6a21\u677f<\/p>\n
PCR \u6bdb\u7ec6\u7ba1\u7535\u6cf3\u6280\u672f\u548cPCR \u9ad8\u5206\u8fa8\u7387\u7194\u89e3\u66f2\u7ebf\u6cd5\u7684\u7ed3\u679c\u5224\u65ad\uff1a\u51fa\u73b02\u4e2a\u53ca\u4ee5\u4e0a\u4e0d\u7a33\u5b9a\u7684\u6838\u82f7\u9178\u91cd\u590d\u4f4d\u70b9\u65f6\uff0c\u5224\u5b9a\u4e3aMSI-H;\u51fa\u73b01\u4e2a\u6216\u672a\u51fa\u73b0\u4e0d\u7a33\u5b9a\u7684\u6838\u82f7\u9178\u91cd\u590d\u4f4d\u70b9\u65f6\uff0c\u5224\u5b9a\u4e3aMSI-L\/MSS\u3002<\/p>\n
\u76ee\u524d\uff0c\u91c7\u7528NGS\u68c0\u6d4bMSI\u7684\u7ed3\u679c\u5224\u65ad\u5c1a\u7f3a\u4e4f\u7edf\u4e00\u6807\u51c6\u3002\u5404\u5b9e\u9a8c\u5ba4\u9700\u6839\u636e\u4e0d\u540c\u68c0\u6d4b\u5e73\u53f0\u548cPanel\u7684\u6027\u80fd\u786e\u8ba4\u8bbe\u5b9aMSI\u9633\u6027\u9608\u503c\u3002<\/p>\n
\u5b9e\u9a8c\u5ba4\u51fa\u5177\u7684\u62a5\u544a\u5185\u5bb9\u9664\u60a3\u8005\u57fa\u672c\u4fe1\u606f\u5916\uff0c\u8fd8\u9700\u4f53\u73b0\u7ec4\u7ec7\u5b66\u75c5\u7406\u8bca\u65ad\u7ed3\u679c\u3001\u80bf\u7624\u7ec6\u80de\u542b\u91cf\u3001DNA\u8d28\u63a7\u4fe1\u606f\u3001\u68c0\u6d4b\u65b9\u6cd5\u3001\u68c0\u6d4b\u4f4d\u70b9\u3001\u68c0\u6d4b\u7ed3\u679c\u3001\u68c0\u6d4b\u7ed3\u8bba\u3001\u7ed3\u679c\u89e3\u91ca\u3001\u6ce8\u610f\u4e8b\u9879\uff08\u53ef\u63cf\u8ff0\u68c0\u6d4b\u6280\u672f\u7684\u5c40\u9650\u6027\u3001\u76f8\u5173\u6ce8\u610f\u4e8b\u9879\uff09\u548c\u53c2\u8003\u6587\u732e\u7b49\uff08\u88681)\u3002\u82e5\u91c7\u7528NGS\u68c0\u6d4bMSI\u72b6\u6001\uff0c\u5219\u9700\u53e6\u5916\u6ce8\u660e\u6d4b\u5e8f\u8d28\u91cf\u8bc4\u4f30\u6307\u6807\u3002<\/p>\n<\/p>\n
\u53c2\u4e0e\u7f16\u5199\u672c\u7248\u5171\u8bc6\u7684\u4e13\u5bb6\u7ec4\u6210\u5458\uff08\u6309\u5355\u4f4d\u548c\u59d3\u6c0f\u62fc\u97f3\u4e3a\u5e8f\uff09\uff1a\u5b89\u5fbd\u533b\u79d1\u5927\u5b66\u7b2c\u4e00\u9644\u5c5e\u533b\u9662\uff08\u6f58\u7f8e\u534e\uff09\uff1b\u5317\u4eac\u5927\u5b66\u533b\u5b66\u90e8\uff0f\u5317 \u4eac\u5927\u5b66\u7b2c\u4e09\u533b\u9662\uff08\u5f20\u71d5\uff09\uff1b\u5317\u4eac\u5927\u5b66\u80bf\u7624\u533b\u9662\uff08\u5468\u7acb\u65b0\uff09\uff1b\u91cd\u5e86\u5e02\u4eba\u6c11\u533b\u9662\uff08\u5218\u747e\uff09\uff1b\u798f\u5efa\u7701\u7acb\u533b\u9662\uff08\u9648\u6615\uff09\uff1b\u798f\u5efa\u7701\u80bf\u7624\u533b\u9662\uff08\u5e08 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