Low frequency of E-cadherin alterations in familial breast cancer

In order to explore the possible role of E-cadherin in familial cancer, 19 familial breast cancer patients, whose tumours demonstrated loss of heteroz ygosity (LOH) at the E-cadherin locus, were screened for germline mutations . No pathogenic germline alterations were detected in these individuals. Ho wever, a somatic mutation was found (49-2A-->C) in one of the tumours. This tumour showed a pattern of both ductal and lobular histology. Another 10 f amilies with cases of breast, gastric and colon cancer were also screened f or germline mutations, and no mutations were found. A missense mutation in exon 12 of E-cadherin (1774G-->A; Ala592Thr) was previously found in one fa mily with diffuse gastric cancer, and colon and breast cancer. An allelic a ssociation study was performed to determine whether the Ala592Thr alteratio n predisposes to breast cancer. In total, we studied 484 familial breast ca ncer patients, 614 sporadic breast cancer patients and 497 control individu als. The frequencies of this alteration were similar in these groups. Howev er, a correlation between the Ala592Thr alteration and ductal comedo-type t umour was seen. These results, together with previously reported studies, i ndicate that germline mutations and, more commonly, somatic mutations in E- cadherin may have an influence on the behaviour of the tumours, rather than predispose to breast cancer.