Berx G, Becker K F, Höfler H, van Roy F
Department of Molecular Biology, V.I.B., University of Gent, Belgium.
Hum Mutat. 1998;12(4):226-37. doi: 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D.
The cell-cell adhesion molecule E-cadherin is well known to act as a strong invasion suppressor in experimental tumor cell systems. Frequent inactivating mutations have been identified for the E-cadherin gene (CDH1) in diffuse gastric cancers and lobular breast cancers. To date, 69 somatic mutations have been reported comprising, in addition to few missense mutations, mainly splice site mutations and truncation mutations caused by insertions, deletions, and nonsense mutations. Interestingly, there is a major difference in mutation type between diffuse gastric and infiltrative lobular breast cancers. In diffuse gastric tumors, the predominant defects are exon skippings, which cause in-frame deletions. By contrast, most mutations found in infiltrating lobular breast cancers are out-of-frame mutations, which are predicted to yield secreted truncated E-cadherin fragments. In most cases, these mutations do occur in combination with loss of heterozygosity (LOH) of the wild-type allele. Inactivating germline mutations of E-cadherin were recently reported for families with early-onset diffuse gastric cancer. Also, at the early stages of sporadic lobular breast and diffuse gastric cancers, E-cadherin mutations were detected, suggesting loss of growth control by such mutations and defining E-cadherin as a true tumor suppressor for these particular tumor types.
细胞间粘附分子E-钙粘蛋白在实验性肿瘤细胞系统中作为一种强大的侵袭抑制因子而广为人知。在弥漫性胃癌和小叶乳腺癌中已发现E-钙粘蛋白基因（CDH1）频繁发生失活突变。迄今为止，已报道了69种体细胞突变，除少数错义突变外，主要是由插入、缺失和无义突变引起的剪接位点突变和截短突变。有趣的是，弥漫性胃癌和浸润性小叶乳腺癌在突变类型上存在重大差异。在弥漫性胃肿瘤中，主要缺陷是外显子跳跃，导致框内缺失。相比之下，浸润性小叶乳腺癌中发现的大多数突变是框外突变，预计会产生分泌性截短的E-钙粘蛋白片段。在大多数情况下，这些突变确实与野生型等位基因的杂合性缺失（LOH）同时发生。最近报道了早发性弥漫性胃癌家族中E-钙粘蛋白的失活种系突变。此外，在散发性小叶乳腺癌和弥漫性胃癌的早期阶段也检测到了E-钙粘蛋白突变，这表明此类突变导致生长控制丧失，并将E-钙粘蛋白定义为这些特定肿瘤类型的真正肿瘤抑制因子。
