Novel BRCA1 and BRCA2 Tumour Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas - Weren - Human Mutation - Wiley Online Library Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Saturday, October 22, 2016

Novel BRCA1 and BRCA2 Tumour Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas - Weren - Human Mutation - Wiley Online Library



 open access pdf (technical)

 For the evaluation of our approach 127 ovarian tumour samples derived from 96 271 patients were tested: 29 with a BRCA1, 14 with a BRCA2 and 53 without a germline mutation 272 in either gene.
 Histology review of the ovarian carcinomas
Histology revision by an expert pathologist revealed that 83% of the carcinomas derived from germline mutation carriers had a high grade serous histology (n=35). The other patients with a germline mutation in BRCA1 or BRCA2 presented carcinomas with a mixed (n=2), high grade endometrioid (n=1), clear cell (n=1) and poorly/undifferentiated (n=3) histology (Supp. Table S6a)......
abstract:
Novel BRCA1 and BRCA2 Tumour Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas
 
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.

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