Analysis of somatic microsatellite indels identifies driver events in human tumors
| Autor: | Gad Getz, Alan D. D'Andrea, Rosa Karlic, Yehuda Brody, Michael S. Lawrence, Yosef E. Maruvka, Andre Bernards, Julian M. Hess, Franziska Michor, Kent W. Mouw, Paz Polak, Lior Z. Braunstein, Prasanna Parasuraman, Atanas Kamburov, Nicholas J. Haradhvala, Adam J. Bass, Amnon Koren, Esther Rheinbay |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Somatic cell Biomedical Engineering Bioengineering Biology medicine.disease_cause Applied Microbiology and Biotechnology Article 03 medical and health sciences INDEL Mutation Neoplasms medicine Humans Exome RNA Messenger Indel Gene Genetics Mutation High-Throughput Nucleotide Sequencing RNA-Binding Proteins food and beverages Microsatellite instability Cancer medicine.disease Cancer genetics Genome informatics 030104 developmental biology MSH3 Molecular Medicine Microsatellite Microsatellite Instability Genes Neoplasm Microsatellite Repeats Biotechnology |
| Zdroj: | Nat Biotechnol |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | Microsatellites (MSs) are tracts of variable-length repeats of short DNA motifs that exhibit high rates of mutation in the form of insertions or deletions (indels) of the repeated motif. Despite their prevalence, the contribution of somatic MS indels to cancer has been largely unexplored, owing to difficulties in detecting them in short-read sequencing data. Here we present two tools: MSMuTect, for accurate detection of somatic MS indels, and MSMutSig, for identification of genes containing MS indels at a higher frequency than expected by chance. Applying MSMuTect to whole-exome data from 6, 747 human tumors representing 20 tumor types, we identified >1, 000 previously undescribed MS indels in cancer genes. Additionally, we demonstrate that the number and pattern of MS indels can accurately distinguish microsatellite-stable tumors from tumors with microsatellite instability, thus potentially improving classification of clinically relevant subgroups. Finally, we identified seven MS indel driver hotspots: four in known cancer genes (ACVR2A, RNF43, JAK1, and MSH3) and three in genes not previously implicated as cancer drivers (ESRP1, PRDM2, and DOCK3). |
| Databáze: | OpenAIRE |
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