Berx G, Cleton-Jansen A M, Strumane K, de Leeuw W J, Nollet F, van Roy F, Cornelisse C
Department of Molecular Biology, Laboratory of Molecular Cell Biology, University of Ghent, Belgium.
Oncogene. 1996 Nov 7;13(9):1919-25.
We have analysed a series of 49 human breast cancers for mutations in the entire coding region plus flanking intron sequences of the E-cadherin gene. The tumours included 41 infiltrating lobular carcinomas, two infiltrating ducto-lobular carcinomas and six infiltrative ductal carcinomas. In the lobular carcinomas 23 different somatic mutations were detected, of which seven were insertions, 11 deletions, two nonsense mutations and three splice site mutations. The other tumours showed no detectable E-cadherin mutations. All the frameshift and nonsense mutations are expected to generate a secreted E-cadherin fragment instead of a transmembrane protein with cell adhesion activity. The majority of the mutations (21 of 23) were found in combination with loss of heterozygosity of the wild type E-cadherin locus (16q22.1), a hallmark of classical tumour suppressor genes. The mutations were scattered over the whole coding region and no hot spots could be identified. All mutations described here were previously unreported. In conclusion, we have identified up to now E-cadherin mutations in 27 of 48 (56%) infiltrating lobular breast carcinomas and in 0 of 50 breast cancers of other histopathological subtypes. These data provide strong evidence that frequent E-cadherin mutations are involved in the particular etiology of sporadic lobular breast cancers.
我们分析了49例人类乳腺癌样本，检测E-钙黏蛋白基因整个编码区及其侧翼内含子序列中的突变情况。这些肿瘤包括41例浸润性小叶癌、2例浸润性导管-小叶癌和6例浸润性导管癌。在小叶癌中检测到23种不同的体细胞突变，其中7种为插入突变，11种为缺失突变，2种为无义突变，3种为剪接位点突变。其他肿瘤未检测到E-钙黏蛋白突变。所有移码突变和无义突变预计会产生一种分泌型E-钙黏蛋白片段，而不是具有细胞黏附活性的跨膜蛋白。大多数突变（23种中的21种）与野生型E-钙黏蛋白基因座（16q22.1）杂合性缺失同时出现，这是经典肿瘤抑制基因的一个标志。这些突变分散在整个编码区，未发现热点区域。这里描述的所有突变以前均未报道。总之，截至目前，我们在48例浸润性小叶乳腺癌中的27例（56%）以及50例其他组织病理学亚型的乳腺癌中的0例中发现了E-钙黏蛋白突变。这些数据提供了有力证据，表明频繁的E-钙黏蛋白突变参与了散发性小叶乳腺癌的特定病因。
