Microsatellite instability differences between familial and sporadic ovarian cancers
Microsatellite instability differences between familial and sporadic ovarian cancers
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DOI：
10.1093/carcin/17.9.1799
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发表时间：
1996-09-01
期刊：
影响因子：
4.7
通讯作者：
Gilbert, F
中科院分区：
文献类型：
--
作者：
Arzimanoglou, II;Lallas, T;Gilbert, F
DNA不稳定性，反映在分裂细胞的短串联重复序列(微卫星)的改变模式中，已在遗传性非息肉病性结肠癌(HNPCC)和其他肿瘤类型中被描述。卵巢癌(OC)，虽然最常见的是散发性癌症，但也可以复发，HNPCC，作为Lynch癌症家族综合征的一部分，在对90例OC患者的微卫星不稳定性(MIN)的研究中，我们发现在3/28(11%)有癌症家族史的OC患者和8/62(13%)无癌症家族史的OC患者中，2/3MIN+OC患者的家族史与Lynch癌症家族综合征一致，我们在肿瘤和正常组织(HNPCC-type of MIN)的微卫星图谱中发现了额外的条带，但两个DNA错配修复基因hMSH2和hMLH1没有胚系突变。在7/8min+散发性OC病例中，发现HNPCC中未见明显的min模式。这些疾病的特点是部分或全部条带移位，导致个别条带数目减少和/或局限于肿瘤的条带强度改变，仅有一例发现hMSH2或hMLH1的胚系改变：随后发现这是一种多态性，另一例发现明显的局限于肿瘤的kMLH1体细胞变化，在MIN+OC病例中，我们没有发现hMSH2和hMLH1(HNPCC的主要突变部位)的种系病理突变，这表明MIN在OC中的遗传基础可能不同于HNPCC；我们发现，不同的微卫星带型在很大程度上区分了散发性和家族性OC，这可能反映了不同的DNA修复基因在个体OC的MIN中的参与。
DNA instability, reflected in altered patterns of short tandem repeat sequences (microsatellites) in dividing cells, has been described in hereditary non-polyposis colon cancer (HNPCC) and in other tumor types. Ovarian cancer (OC), although most often a sporadic cancer, can recur, with HNPCC, as part of the Lynch cancer family syndrome, In an investigation of microsatellite instability (MIN) in 90 OC cases, we found MIN in 3/28 (11%) OC cases with, and 8/62 (13%) without, a family history of cancer, For 2/3 MIN+ OC cases with family cancer history consistent with the Lynch cancer family syndrome, we found additional bands in the microsatellite patterns in tumor versus normal tissue (HNPCC-type of MIN), but no germline mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. In 7/8 MIN+ sporadic OC cases distinct MIN patterns not commonly reported in HNPCC were found. These are characterized by partial or total band shifting, leading to fewer bands and/or changes in the intensity of individual bands restricted to the tumor, In only one case was a germline change in hMSH2 or hMLH1 identified: this was subsequently found to be a polymorphism, An apparent kMLH1 somatic change confined to the tumor was found in another case, The fact that we found no germline pathologic mutations in hMSH2 and hMLH1 (predominant sites of mutation in HNPCC) in MIN+ OC cases, suggests that the genetic basis of MIN in OC can be different from that in HNPCC; our finding that distinct microsatellite banding patterns largely distinguish sporadic from familial OC, may reflect the involvement of different DNA repair genes in MIN in individual OC cases.