title: Sequence-based detection of mutations in cadherin 1 to determine the prevalence of germline mutations in patients with invasive lobular carcinoma of the breast.
abstract: 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.
authors: Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA, USA.
authors: Allyson L
authors: AL
authors: Valente
authors: Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA, USA.
authors: Seth
authors: S
authors: Rummel
authors: Clinical Breast Care Project, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD, USA.
authors: Craig D
authors: CD
authors: Shriver
authors: Clinical Breast Care Project, Henry M. Jackson Foundation for the Advancement of Military Medicine, 620 Seventh Street, Windber, PA, USA.
authors: Rachel E
authors: RE
authors: Ellsworth
keywords: Breast cancer; CDH1; ILCA