Title | Allele-specific genomic data elucidate the role of somatic gain and copy-number neutral loss of heterozygosity in cancer. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Ciani Y, Fedrizzi T, Prandi D, Lorenzin F, Locallo A, Gasperini P, Franceschini GMarco, Benelli M, Elemento O, Fava LL, Inga A, Demichelis F |
Journal | Cell Syst |
Volume | 13 |
Issue | 2 |
Pagination | 183-193.e7 |
Date Published | 2022 Feb 16 |
ISSN | 2405-4720 |
Keywords | Alleles, Genomics, Humans, Loss of Heterozygosity, Neoplasms |
Abstract | Pan-cancer studies sketched the genomic landscape of the tumor types spectrum. We delineated the purity- and ploidy-adjusted allele-specific profiles of 4,950 patients across 27 tumor types from the Cancer Genome Atlas (TCGA). Leveraging allele-specific data, we reclassified as loss of heterozygosity (LOH) 9% and 7% of apparent copy-number wild-type and gain calls, respectively, and overall observed more than 18 million allelic imbalance somatic events at the gene level. Reclassification of copy-number events revealed associations between driver mutations and LOH, pointing out the timings between the occurrence of point mutations and copy-number events. Integrating allele-specific genomics and matched transcriptomics, we observed that allele-specific gene status is relevant in the regulation of TP53 and its targets. Further, we disclosed the role of copy-neutral LOH in the impairment of tumor suppressor genes and in disease progression. Our results highlight the role of LOH in cancer and contribute to the understanding of tumor progression. |
DOI | 10.1016/j.cels.2021.10.001 |
Alternate Journal | Cell Syst |
PubMed ID | 34731645 |
PubMed Central ID | PMC8856743 |
Grant List | P50 CA211024 / CA / NCI NIH HHS / United States |