Tumour BRCA1/2 mutation testing in Platinum sensitive relapsed ovarian cancer patients

Introduction

Patients with platinum sensitive relapsed ovarian cancer and germline or somatic mutations in BRCA1/2 may benefit from treatment with the poly ADP ribose polymerase (PARP) inhibitor Lynparza (Olaparib). BRCA1/2 mutation screening in FFPE tissue can identify patients with somatic BRCA1/2 mutations who may benefit from targeted therapy. The test has been designed to perform on DNA extracted from formalin fixed paraffin embedded (FFPE) tissue specimens and detect somatic mutations in samples with neoplastic cell content >20%.

Referral information

We require a minimum 5x5µM thick unstained sections from a pathology specimen which must have been reviewed by a histopathologist and be accompanied by a completed test request form, clearly stating the proportion of neoplastic cells in the block. For optimum detection of somatic mutations >20% neoplastic cell content is required. Referrals will be accepted from oncologists, pathologists, geneticists and MDTs managing patients with platinum sensitive relapsed ovarian cancer.

Price & reporting times

Test Price (NHS) Price (non-NHS) TRT
FFPE pathology samples POA POA 28 cd

Test validation & quality assurance - information for users

The FFPE BRCA mutation screen has been validated in-house using DNA extracted from over 50 FFPE tissue samples, 26 of which were known to carry BRCA1/2 mutations or variants and in two multi-centre studies where in total >20 samples were tested blind. Analytical test sensitivity is >98%, analytical test specificity is >99%. Data is analysed using a custom bioinformatics pipeline developed in-house which is capable of detecting germline and somatic mutations present at a level of >4% mutant allele frequency in the sample submitted for testing. Poor preservation of DNA or low DNA yield may lead to analysis failure which occurs in <20% of samples analysed. This test is not intended to substitute for germline BRCA1/2 mutation screening in patients at high risk of having a BRCA1/2 mutation as it is not designed to detect large deletions or duplications.

Sample requirements

5 x 5µM FFPE unstained slide mounted sections (without coverslips) from a tissue block selected to have maximum neoplastic cell content. If neoplastic cell content is less than 20% and the sample is suitable for macrodissection, please send an accompanying H&E stained guide slide prepared from a neighbouring section with the region of neoplasia clearly marked out. Where neoplastic cell content is greater than 30%, 5 x 5 µM FFPE sections as unmounted scrolls in a clean, unused, tube or container manufactured under aseptic conditions is acceptable.

Referral guidelines

Please see our referral guidelines for more information.

OMIM Number(s) - 604370, 612555

Gene(s) - BRCA1, BRCA2

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