domingo, 30 de octubre de 2016

Novel BRCA1 and BRCA2 Tumour Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas. - PubMed - NCBI

Novel BRCA1 and BRCA2 Tumour Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas. - PubMed - NCBI



 2016 Oct 21. doi: 10.1002/humu.23137. [Epub ahead of print]

Novel BRCA1 and BRCA2 Tumour Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas.

Abstract

With the recent introduction of Poly(ADP-ribose) polymerase (PARP) inhibitors, a promising novel therapy has become available for ovarian carcinoma patients with inactivating BRCA1 or BRCA2 mutations in their tumour. To select patients who may benefit from these treatments, assessment of the mutation status of BRCA1 and BRCA2 in the tumour is required. For reliable evaluation of germline and somatic mutations in these genes in DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue, we have developed a single molecule molecular inversion probe (smMIP)-based targeted next generation sequencing (NGS) approach. Our smMIP-based NGS approach provides analysis of both strands of the open-reading frame of BRCA1 and BRCA2, enabling the discrimination between real variants and formalin induced artefacts. The single molecule tag enables compilation of unique reads leading to a high analytical sensitivity and enabling assessment of the reliability of mutation-negative results. MLPA and MS-MLPA were used to detect exon deletions of BRCA1 and methylation of the BRCA1 promoter, respectively. Here, we show that this combined approach allows the rapid and reliable detection of both germline and somatic aberrations affecting BRCA1 and BRCA2 in DNA derived from FFPE ovarian carcinomas, enabling improved hereditary cancer risk assessment and clinical treatment of ovarian cancer patients. This article is protected by copyright. All rights reserved.

KEYWORDS:

BRCA testing; BRCA1; BRCA2; Ovarian cancer; PARP-inhibitor; cancer predisposition; personalized medicine; single molecule molecular inversion probes

PMID:
 
27767231
 
DOI:
 
10.1002/humu.23137

[PubMed - as supplied by publisher]

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