BMC medical genomics, 2017-05, Vol.10 (1), p.33-33, Article 33
2017
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- Autor(en) / Beteiligte
- Titel
- Comprehensive detection of germline variants by MSK-IMPACT, a clinical diagnostic platform for solid tumor molecular oncology and concurrent cancer predisposition testing
- Ist Teil von
- BMC medical genomics, 2017-05, Vol.10 (1), p.33-33, Article 33
- Ort / Verlag
- England: BioMed Central
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The growing number of Next Generation Sequencing (NGS) tests is transforming the routine clinical diagnosis of hereditary cancers. Identifying whether a cancer is the result of an underlying disease-causing mutation in a cancer predisposition gene is not only diagnostic for a cancer predisposition syndrome, but also has significant clinical implications in the clinical management of patients and their families. Here, we evaluated the performance of MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) in detecting genetic alterations in 76 genes implicated in cancer predisposition syndromes. Output from hybridization-based capture was sequenced on an Illumina HiSeq 2500. A custom analysis pipeline was used to detect single nucleotide variants (SNVs), small insertions/deletions (indels) and copy number variants (CNVs). MSK-IMPACT detected all germline variants in a set of 233 unique patient DNA samples, previously confirmed by previous single gene testing. Reproducibility of variant calls was demonstrated using inter- and intra- run replicates. Moreover, in 16 samples, we identified additional pathogenic mutations other than those previously identified through a traditional gene-by-gene approach, including founder mutations in BRCA1, BRCA2, CHEK2 and APC, and truncating mutations in TP53, TSC2, ATM and VHL. This study highlights the importance of the NGS-based gene panel testing approach in comprehensively identifying germline variants contributing to cancer predisposition and simultaneous detection of somatic and germline alterations.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1755-8794eISSN: 1755-8794DOI: 10.1186/s12920-017-0271-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_972eab9f9a884f718c0b98031b307246
- Format
- –
- Schlagworte
- Adenomatous polyposis coli, Adenomatous Polyposis Coli Protein - genetics, Ataxia Telangiectasia Mutated Proteins - genetics, Bioinformatics, Biomarkers, Tumor - genetics, BRCA1 protein, BRCA1 Protein - genetics, BRCA2 protein, BRCA2 Protein - genetics, Cancer, Cancer Predisposition, Checkpoint Kinase 2 - genetics, Copy number, Deoxyribonucleic acid, DNA, DNA Copy Number Variations, DNA Mutational Analysis - methods, Genes, Genetic Predisposition to Disease, Genetic testing, Genomes, Genomics, Germ-Line Mutation, Germline Mutation, Haplotypes, Hereditary Cancer Syndrome, Humans, Hybridization, Laboratories, Lynch Syndrome, Mutation, Neoplasm Proteins - genetics, Neoplasms - genetics, Neoplasms - metabolism, p53 Protein, Pathogenic Variant, Polymorphism, Single Nucleotide, Reproducibility of Results, Technical Advance, Tuberous Sclerosis Complex 2, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Proteins - genetics, VHL protein, Von Hippel-Lindau Tumor Suppressor Protein - genetics