Transcriptional effects of copy number alterations in a large set of human cancers

被引：56

作者：

Bhattacharya, Arkajyoti ^{[1
]}

Bense, Rico D. ^{[1
]}

Urzua-Traslavina, Carlos G. ^{[1
]}

de Vries, Elisabeth G. E. ^{[1
]}

van Vugt, Marcel A. T. M. ^{[1
]}

Fehrmann, Rudolf S. N. ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

欧洲研究理事会;

关键词：

DOSAGE SENSITIVITY; GENE; SIGNATURES; GENOMICS; IMPACT; INSTABILITY; PATTERNS; HALLMARK;

D O I：

10.1038/s41467-020-14605-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Copy number alterations (CNAs) can promote tumor progression by altering gene expression levels. Due to transcriptional adaptive mechanisms, however, CNAs do not always translate proportionally into altered expression levels. By reanalyzing >34,000 gene expression profiles, we reveal the degree of transcriptional adaptation to CNAs in a genome-wide fashion, which strongly associate with distinct biological processes. We then develop a platform-independent method-transcriptional adaptation to CNA profiling (TACNA profiling)-that extracts the transcriptional effects of CNAs from gene expression profiles without requiring paired CNA profiles. By applying TACNA profiling to >28,000 patient-derived tumor samples we define the landscape of transcriptional effects of CNAs. The utility of this landscape is demonstrated by the identification of four genes that are predicted to be involved in tumor immune evasion when transcriptionally affected by CNAs. In conclusion, we provide a novel tool to gain insight into how CNAs drive tumor behavior via altered expression levels.

引用

页数：12

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