Accession Number : ADA613322

Title :   Identification of Variants in Breast Cancer Susceptibility Genes and Determination of Functional and Clinical Significance of Novel Mutations

Descriptive Note : Annual rept. 30 Sep 2013-29 Sep 2014


Personal Author(s) : Maxwell, Kara N

Full Text :

Report Date : Oct 2014

Pagination or Media Count : 55

Abstract : Purpose: Clinical testing for germline variation in multiple cancer susceptibility genes is available using massively parallel sequencing. Limited information is available for pre-test genetic counseling regarding the spectrum of mutations and variants of uncertain significance (VUSs) in defined patient populations. Methods: We performed massively parallel sequencing using targeted capture of 22 cancer susceptibility genes in 278 BRCA1/2 negative patients with early onset breast cancer (diagnosed under age 40). Results: Thirty-one patients (11%) were found to have at least one deleterious or likely deleterious variant. Seven patients (2.5% overall) were found to have deleterious or likely deleterious variants in genes for which clinical guidelines exist for management, namely TP53 (4), CDKN2A (1) MSH2 (1), and MUTYH (double heterozygote). Twenty-four patients (8.6%) had deleterious or likely deleterious variants in a cancer susceptibility gene for which clinical guidelines are lacking, such as CHEK2 and ATM. Fifty-four patients (19%) had at least one VUS, and six patients were heterozygous for a variant in MUTYH. Conclusion: These data demonstrate that massively parallel sequencing identifies reportable variants in known cancer susceptibility genes in over 30% of patients with early onset breast cancer. However, only rare patients (2.5%) have definitively actionable mutations given current clinical management guidelines.


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE