[HTML][HTML] Comprehensive detection of germline variants by MSK-IMPACT, a clinical diagnostic platform for solid tumor molecular oncology and concurrent cancer …
DT Cheng, M Prasad, Y Chekaluk, R Benayed… - BMC medical …, 2017 - Springer
BMC medical genomics, 2017•Springer
Background 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. Methods Here,
we evaluated the performance of MSK-IMPACT (Memorial Sloan Kettering-Integrated …
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. Methods Here,
we evaluated the performance of MSK-IMPACT (Memorial Sloan Kettering-Integrated …
Background
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.
Methods
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).
Results
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.
Conclusions
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.
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