| Title: |
Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors |
| Authors: |
Michael B. Mumphrey, Noshad Hosseini, Abhijit Parolia, Jie Geng, Weiping Zou, Malini Raghavan, Arul Chinnaiyan, Marcin Cieslik |
| Source: |
Cell Reports, Vol 42, Iss 8, Pp 112965- (2023) |
| Publisher Information: |
Elsevier, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CP: Cancer, CP: Immunology, Biology (General), QH301-705.5 |
| More Details: |
Summary: Disruption of antigen presentation via loss of major histocompatibility complex (MHC) expression is a strategy whereby cancer cells escape immune surveillance and develop resistance to immunotherapy. Here, we develop the personalized genomics algorithm Hapster and accurately call somatic mutations within the MHC genes of 10,001 primary and 2,199 metastatic tumors, creating a catalog of 1,663 non-synonymous mutations that provide key insights into MHC mutagenesis. We find that MHC class I genes are among the most frequently mutated genes in both primary and metastatic tumors, while MHC class II mutations are more restricted. Recurrent deleterious mutations are found within haplotype- and cancer-type-specific hotspots associated with distinct mutational processes. Functional classification of MHC residues reveals significant positive selection for mutations disruptive to the B2M, peptide, and T cell binding interfaces, as well as to MHC chaperones. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124723009762; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112965 |
| Access URL: |
https://doaj.org/article/d0c6d870f1f846c894747d75024f6dd8 |
| Accession Number: |
edsdoj.0c6d870f1f846c894747d75024f6dd8 |
| Database: |
Directory of Open Access Journals |
