期刊
CELL
卷 168, 期 3, 页码 460-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.12.025
关键词
-
资金
- National Cancer Institute as part of The Cancer Genome Atlas project [U24CA126546, U24CA143867, U24CA143845, U24CA126544, U24CA143883]
- Department of Defense [W81XWH-12-1-0269]
- American Cancer Society Research Professor Award
- National Cancer Institute [R35CA197568]
- Burroughs- Wellcome Career Award
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据