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Dynamic changes of driver genes' mutations across clinical stages in nine cancer types.

Authors
  • Li, Xia1
  • 1 Laboratory for Gene and Cell Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, China. , (China)
Type
Published Article
Journal
Cancer Medicine
Publisher
Wiley
Publication Date
Jul 01, 2016
Volume
5
Issue
7
Pages
1556–1565
Identifiers
DOI: 10.1002/cam4.704
PMID: 26992457
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The driver genes play critical roles for tumorigenesis, and the number of identified driver genes reached plateau. But how they act during different cancer development stages is lack of knowledge. We investigated 138 driver genes' mutation changes across clinical stages using 3,477 cases in nine cancer types from the Cancer Genome Atlas (TCGA) and constructed their temporal order relationships. We also examined the codon changes for the widely mutated TP53 and PIK3CA in tumor stages. Combinations of one to three driver genes specifically dominated in each cancer. Across the clinical stages, we categorized three patterns for the behaviors of driver genes' mutation changes in the nine cancer types: recurrently mutated in all the stages and triggering other mutations; certain mutations lost meanwhile other mutations emerged; mutations dominated across entire stages, while other mutations gradually appeared or disappeared. We observed different codon changes dominated in different stages and revealed mutations recurrently occurring on the hotspot regions of the coding sequence may be the core factor for driver genes' tumorigenesis. Our results highlighted the dynamic changes of oncogenesis roles in different clinical stages and suggested different diagnostic decision making according to the clinical stages of patients. © 2016 The Author. Cancer Medicine published by John Wiley & Sons Ltd.

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