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Type of publication: Journal Article
Type of document: Full Paper

Year: 2017

Authors: Balendran, S; Liebmann-Reindl, S; Berghoff, AS; Reischer, T; Popitsch, N; Geier, CB; Kenner, L; Birner, P; Streubel, B; Preusser, M

Title: Next-Generation Sequencing-based genomic profiling of brain metastases of primary ovarian cancer identifies high number of BRCA-mutations.

Source: J Neurooncol. 2017; 133(3):469-476

Authors Vetmeduni Vienna:

Kenner Lukas

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals

Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases (BM). In this study, we evaluated the mutational profile of ovarian cancer metastases through Next-Generation Sequencing (NGS) with the aim of identifying potential clinically actionable genetic alterations with options for small molecule targeted therapy. Library preparation was conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of variant alterations, each with unique molecular profiles. The 37 identified variants were distributed over 22 cancer-related genes (23.4%). The number of mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM samples showed mutations in at least one DNA repair gene. Our NGS study of BM of ovarian carcinoma revealed a significant number of BRCA-mutations beside TP53, ATM and CHEK2 mutations. These findings strongly suggest the implication of BRCA and DNA repair malfunction in ovarian cancer metastasizing to the brain. Based on these findings, pharmacological PARP inhibition could be one potential targeted therapeutic for brain metastatic ovarian cancer patients.

Keywords Pubmed: Adult
Ataxia Telangiectasia Mutated Proteinsgenetics
BRCA1 Proteingenetics
BRCA2 Proteingenetics
Brain Neoplasmsgeneticssecondary
High-Throughput Nucleotide Sequencing
Middle Aged
Ovarian Neoplasmsdrug therapygeneticspathology
Retrospective Studies
Tumor Suppressor Protein p53genetics

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