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Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity
- Source :
- Nature biotechnology
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Mutational hotspots indicate selective pressure across a population of tumor samples, but their prevalence within and across cancer types is incompletely characterized. An approach to detect significantly mutated residues, rather than methods that identify recurrently mutated genes, may uncover new biologically and therapeutically relevant driver mutations. Here we developed a statistical algorithm to identify recurrently mutated residues in tumour samples. We applied the algorithm to 11,119 human tumors, spanning 41 cancer types, and identified 470 hotspot somatic substitutions in 275 genes. We find that half of all human tumors possess one or more mutational hotspots with widespread lineage-, position-, and mutant allele-specific differences, many of which are likely functional. In total, 243 hotspots were novel and appeared to affect a broad spectrum of molecular function, including hotspots at paralogous residues of Ras-related small GTPases RAC1 and RRAS2. Redefining hotspots at mutant amino acid resolution will help elucidate the allele-specific differences in their function and could have important therapeutic implications.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Lineage (genetic)
DNA Mutational Analysis
genetic processes
information science
Biomedical Engineering
Bioengineering
Biology
medicine.disease_cause
Applied Microbiology and Biotechnology
Article
03 medical and health sciences
Neoplasms
medicine
Humans
Genetics
Mutation
business.industry
Extramural
Computational Biology
food and beverages
Cancer
medicine.disease
3. Good health
Human tumor
030104 developmental biology
Molecular Medicine
Personalized medicine
business
Algorithms
Biotechnology
Subjects
Details
- ISSN :
- 15461696 and 10870156
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Nature Biotechnology
- Accession number :
- edsair.doi.dedup.....30129b2a1d0d528e1298d935c7483574