Paper Info
Title
Protein Domain-Level Landscape Of Cancer-Type-Specific Somatic Mutations
Abstract
Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level.
Year
DOI
Venue
2015
10.1371/journal.pcbi.1004147
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
protein domains,somatic mutation,mutation
Genome,Protein domain,Biology,Breast cancer,Bioinformatics,DNA Mutational Analysis,Germline mutation,Genetics,Colorectal cancer,Cancer,Mutation
Journal
Volume
Issue
ISSN
11
3
1553-734X
Citations 
PageRank 
References 
5
0.49
12
Authors
6
Name
Order
Citations
PageRank
Fan Yang150.49
Evangelia Petsalaki271.61
Thomas Rolland380.87
David E Hill4162.23
Marc Vidal5988.84
Frederick P Roth634534.18