Sequence-based detection of mutations in cadherin 1 to determine the prevalence of germline mutations in patients with invasive lobular carcinoma of the breast

Hereditary Cancer in Clinical Practice

Rachel E Ellsworth³  Craig D Shriver²  Seth Rummel¹  Allyson L Valente¹ 

[1] Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA, USA;Clinical Breast Care Project, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD, USA;Clinical Breast Care Project, Henry M. Jackson Foundation for the Advancement of Military Medicine, 620 Seventh Street, Windber, PA, USA

关键词: CDH1;    ILCA;    Breast cancer;   

Others  :  1140078
DOI  :  10.1186/1897-4287-12-17

 received in 2014-04-14, accepted in 2014-07-11,  发布年份 2014

【 摘 要 】

Background

Loss of cadherin 1 (CDH1) expression, which is normally involved in cell adhesion and maintenance of tissue architecture, is a hallmark of invasive lobular carcinoma (ILCA). Because hereditary cancers may require different risk reduction, counseling and treatment options than sporadic cancer, it is critical to determine the prevalence of germline CDH1 mutations in patients with ILCA.

Methods

All patients with ILCA (n = 100) previously enrolled in the Clinical Breast Care Project were identified. Genomic DNA was isolated from peripheral blood samples and DNA variants were detected for each exon of CDH1 using high-resolution melting technology followed by direct sequencing.

Results

Within the 100 samples screened, four nonsynonymous variants were detected: A592T in one Hispanic patient, A617T in two patients, both African American, P825L in a Causasian patient whose grandmother had stomach cancer, and G879S in a Caucasian patient. Further evaluation of A617T in an additional 165 African American patients found that 11 patients, none with ILCA, carried this variant including one patient who was homozygous for the variant.

Conclusions

CDH1 mutations are infrequent in patients with ILCA, and the variants that were detected have been classified as non-pathogenic. These data suggest that ILCA does not have a significant hereditary component and do not support CDH1 gene mutation testing in patients with ILCA.

【 授权许可】

   
2014 Valente et al.; licensee BioMed Central Ltd.

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