Campus Units
Statistics
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
11-2015
Journal or Book Title
Nature Biotechnology
Volume
33
Issue
11
First Page
1152
Last Page
1158
DOI
10.1038/nbt.3344
Abstract
Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations are enriched for likely functional mutations, including putative loss-of-function events. Recurrence of mutations suggested that these 'hotspot' sites were positively selected. Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes, supporting immune evasion by altered HLA function as a contributory mechanism in cancer.
Copyright Owner
Nature America, Inc.
Copyright Date
2015
Language
en
File Format
application/pdf
Recommended Citation
Shukla, Sachet A.; Rooney, Michael S.; Rajasagi, Mohini; Tiao, Grace; Dixon, Philip M.; Lawrence, Michael S.; Stevens, Jonathan; Lane, William J.; Dellagatta, Jamie L.; Steelman, Scott; Sougnez, Carrie; Cibulskis, Kristian; Kiezun, Adam; Brusic, Vladimir; Wu, Catherine J.; and Getz, Gad, "Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes" (2015). Statistics Publications. 159.
https://lib.dr.iastate.edu/stat_las_pubs/159
Comments
This is a manucript of an article published as Shukla, Sachet A., Michael S. Rooney, Mohini Rajasagi, Grace Tiao, Philip M. Dixon, Michael S. Lawrence, Jonathan Stevens et al. "Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes." Nature biotechnology 33, no. 11 (2015): 1152. doi: 10.1038/nbt.3344. Posted with permission.