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Novel BRCA1 and BRCA2 Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas.
- Source :
-
Human mutation [Hum Mutat] 2017 Feb; Vol. 38 (2), pp. 226-235. Date of Electronic Publication: 2016 Nov 09. - Publication Year :
- 2017
-
Abstract
- With the recent introduction of Poly(ADP-ribose) polymerase inhibitors, a promising novel therapy has become available for ovarian carcinoma (OC) patients with inactivating BRCA1 or BRCA2 mutations in their tumor. To select patients who may benefit from these treatments, assessment of the mutation status of BRCA1 and BRCA2 in the tumor 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. Multiplex ligation-dependent probe amplification (MLPA) and Methylation-specific multiplex ligation-dependent probe amplification (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 OCs, enabling improved hereditary cancer risk assessment and clinical treatment of ovarian cancer patients.<br /> (© 2016 The Authors. **Human Mutation published by Wiley Periodicals, Inc.)
- Subjects :
- Alleles
Amino Acid Substitution
DNA Copy Number Variations
DNA Mutational Analysis
Disease Management
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Testing methods
Genetic Testing standards
Genotype
Germ-Line Mutation
Humans
Loss of Heterozygosity
Ovarian Neoplasms diagnosis
Ovarian Neoplasms therapy
Reproducibility of Results
Clinical Decision-Making
Genes, BRCA1
Genes, BRCA2
Genetic Counseling
Ovarian Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 38
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 27767231
- Full Text :
- https://doi.org/10.1002/humu.23137