Next-generation sequencing for diagnosis of patients with hereditary breast and ovarian cancer

7^th Global Summit on Cancer Therapy

October 05-07, 2015 Dubai, UAE

Bhai Pratibha, Gupta Deepti, Saxena Renu and Verma I C

Sir Ganga Ram Hospital, India

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

BRCA1 and BRCA2 genes are the two most commonly mutated genes in families with Hereditary Breast and Ovarian Cancer (HBOC). However several additional breast cancer predisposition genes are now known to be associated with HBOC. Parallel sequencing of these multiple genes is possible with customized next generation sequencing panels. In the present study we evaluated twenty breast cancer patients with positive family history of breast and ovarian cancer were subjected to high throughput next generation sequencing panel testing. Genes analyzed in the panel are ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1,MRE11A,MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD50, RAD51C, STK11 and TP53. Mutations identified by NGS were validated using Sanger sequencing. Software analyses by Polyphen-2, SIFT, Mutation Taster and Align-GVGD was done to predict damaging effect of novel variants. Predictive genetic testing and counseling was done for the first degree relatives. Pathogenic mutations in 7 out of 20 patients (35%) were identified. In rest of the seven patients we found several variants of unknown significance (VUS). Four patients had mutations in BRCA1 gene (c.5074+1G>A, c.4484+1G>A, c.4552C>C/T p.Q1518Ter, c.7480C>T; R2494X) and one patient had mutation in BRCA2 gene (c.9215T>A p.Val3072Glu). One of the patients had a novel nonsense mutation in MRE11 gene (c.1090C>T: p.Arg364Ter). Another patient was a double heterozygote for mutations in MSH6 and BARD1 gene. In silico analysis, segregation study in the family and 100 normal controls were studied to confirm the pathogenicity of novel mutations. Multi-gene parallel sequencing allowed more effective and accurate diagnosis of HBOC families and supports incorporation of panel testing into clinical practice. Clinical genetic counseling for patients with novel variants and VUS in intermediate penetrance gene is complex and challenging and further studies are needed to clarify the precise management of these patients.

Biography :

Email: pratibha13mar@rediffmail.com