Aaltonen L A, Peltomäki P, Mecklin J P, Järvinen H, Jass J R, Green J S, Lynch H T, Watson P, Tallqvist G, Juhola M
Department of Medical Genetics, University of Helsinki, Finland.
Cancer Res. 1994 Apr 1;54(7):1645-8.
A replication error (RER) phenotype has been documented both in sporadic colorectal tumors and in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). In the current study 8 of 49 (16%) sporadic colorectal cancers (CRCs) and 25 of 29 (86%) CRCs from HNPCC patients were found to be RER+. All 9 (100%) CRCs from HNPCC patients with germline mutations of the mismatch repair gene MSH2 were found to be RER+, while 16 of 20 CRCs from HNPCC kindreds unlinked or not studied for linkage to MSH2 were RER+. Corresponding analysis in colorectal adenomas revealed that only 1 of 33 (3%) sporadic tumors but 8 of 14 (57%) HNPCC tumors were RER+. Moreover, RER was found in all 6 extracolonic cancers (endometrium, 2; kidney, 1; stomach, 1; duodenum, 1; and ovary, 1) derived from members of HNPCC families. These data suggest the involvement of mismatch repair deficiency in the premalignant stage of tumorigenesis in HNPCC cases, and suggest that mismatch repair genes (MSH2 or others) are defective in the germline of nearly all these patients.
复制错误（RER）表型已在散发性结直肠癌肿瘤以及遗传性非息肉病性结直肠癌（HNPCC）患者的肿瘤中得到记录。在当前研究中，49例散发性结直肠癌（CRC）中有8例（16%）以及29例HNPCC患者的CRC中有25例（86%）被发现为RER阳性。所有9例（100%）来自错配修复基因MSH2种系突变的HNPCC患者的CRC均为RER阳性，而来自未与MSH2连锁或未研究与MSH2连锁关系的HNPCC家族的20例CRC中有16例为RER阳性。在结直肠腺瘤中的相应分析显示，33例散发性肿瘤中只有1例（3%）为RER阳性，但14例HNPCC肿瘤中有8例（57%）为RER阳性。此外，在源自HNPCC家族成员的所有6例结外癌症（子宫内膜癌2例；肾癌1例；胃癌1例；十二指肠癌1例；卵巢癌1例）中均发现了RER。这些数据表明错配修复缺陷参与了HNPCC病例肿瘤发生的癌前阶段，并表明几乎所有这些患者的种系中错配修复基因（MSH2或其他基因）存在缺陷。
