Insertions and Deletions Target Lineage-Defining Genes in Human Cancers Academic Article uri icon

Overview

MeSH Major

  • Cell Lineage
  • INDEL Mutation
  • Mutation
  • Neoplasms

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.

publication date

  • January 26, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5564321

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2016.12.025

PubMed ID

  • 28089356

Additional Document Info

start page

  • 460

end page

  • 472.e14

volume

  • 168

number

  • 3