Research article

Low frequency of E-cadherin alterations in familial breast cancer

Sima Salahshor¹, Lei Haixin², Huagang Huo¹, Vessela N Kristensen³, Niklas Loman⁴, Sara Sjöberg-Margolin¹, Åke Borg⁴, Anne-Lise Børresen-Dale³, Igor Vorechovsky² and Annika Lindblom¹

¹  Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden

²  Department of Biosciences at NOVUM, Karolinska Institute, Stockholm, Sweden

³  Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

⁴  Department of Oncology, University Hospital, Lund, Sweden

author email corresponding author email

Breast Cancer Res 2001, 3:199-207doi:10.1186/bcr295

Published:	9 March 2001

Abstract

In order to explore the possible role of E-cadherin in familial cancer, 19 familial breast cancer patients, whose tumours demonstrated loss of heterozygosity (LOH) at the E-cadherin locus, were screened for germline mutations. No pathogenic germline alterations were detected in these individuals. However, 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 families with cases of breast, gastric and colon cancer were also screened for germline mutations, and no mutations were found. A missense mutation in exon 12 of E-cadherin (1774G→A; Ala592Thr) was previously found in one family with diffuse gastric cancer, and colon and breast cancer. An allelic association study was performed to determine whether the Ala592Thr alteration predisposes to breast cancer. In total, we studied 484 familial breast cancer patients, 614 sporadic breast cancer patients and 497 control individuals. The frequencies of this alteration were similar in these groups. However, a correlation between the Ala592Thr alteration and ductal comedo-type tumour was seen. These results, together with previously reported studies, indicate 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.