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Cell DOI:10.1016/j.cell.2016.12.025

Insertions and Deletions Target Lineage-Defining Genes in Human Cancers.

Publication TypeJournal Article
Year of Publication2017
AuthorsImielinski, M, Guo, G, Meyerson, M
JournalCell
Volume168
Issue3
Pages460-472.e14
Date Published2017 Jan 26
ISSN1097-4172
Abstract

Certain cell types function as factories, secreting large quantities of one or more proteins that are central to the physiology of the respective organ. Examples include surfactant proteins in lung alveoli, albumin in liver parenchyma, and lipase in the stomach lining. Whole-genome sequencing analysis of lung adenocarcinomas revealed noncoding somatic mutational hotspots near VMP1/MIR21 and indel hotspots in surfactant protein genes (SFTPA1, SFTPB, and SFTPC). Extrapolation to other solid cancers demonstrated highly recurrent and tumor-type-specific indel hotspots targeting the noncoding regions of highly expressed genes defining certain secretory cellular lineages: albumin (ALB) in liver carcinoma, gastric lipase (LIPF) in stomach carcinoma, and thyroglobulin (TG) in thyroid carcinoma. The sequence contexts of indels targeting lineage-defining genes were significantly enriched in the AATAATD DNA motif and specific chromatin contexts, including H3K27ac and H3K36me3. Our findings illuminate a prevalent and hitherto unrecognized mutational process linking cellular lineage and cancer.

DOI10.1016/j.cell.2016.12.025
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28089356?dopt=Abstract

Alternate JournalCell
PubMed ID28089356