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

Author

Listed:
  • Arkajyoti Bhattacharya

    (University of Groningen)

  • Rico D. Bense

    (University of Groningen)

  • Carlos G. Urzúa-Traslaviña

    (University of Groningen)

  • Elisabeth G. E. Vries

    (University of Groningen)

  • Marcel A. T. M. Vugt

    (University of Groningen)

  • Rudolf S. N. Fehrmann

    (University of Groningen)

Abstract

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.

Suggested Citation

  • Arkajyoti Bhattacharya & Rico D. Bense & Carlos G. Urzúa-Traslaviña & Elisabeth G. E. Vries & Marcel A. T. M. Vugt & Rudolf S. N. Fehrmann, 2020. "Transcriptional effects of copy number alterations in a large set of human cancers," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14605-5
    DOI: 10.1038/s41467-020-14605-5
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    Cited by:

    1. Qilin Zhang & Ziyan Xu & Rui Han & Yunzhi Wang & Zhen Ye & Jiajun Zhu & Yixin Cai & Fan Zhang & Jiangyan Zhao & Boyuan Yao & Zhaoyu Qin & Nidan Qiao & Ruofan Huang & Jinwen Feng & Yongfei Wang & Wenti, 2024. "Proteogenomic characterization of skull-base chordoma," Nature Communications, Nature, vol. 15(1), pages 1-32, December.
    2. Yi-Yu Chen & Jing-Yu Ge & Si-Yuan Zhu & Zhi-Ming Shao & Ke-Da Yu, 2022. "Copy number amplification of ENSA promotes the progression of triple-negative breast cancer via cholesterol biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Dario Zimmerli & Chiara S. Brambillasca & Francien Talens & Jinhyuk Bhin & Renske Linstra & Lou Romanens & Arkajyoti Bhattacharya & Stacey E. P. Joosten & Ana Moises Silva & Nuno Padrao & Max D. Welle, 2022. "MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Filipe Correia Martins & Dominique-Laurent Couturier & Ines Santiago & Carolin Margarethe Sauer & Maria Vias & Mihaela Angelova & Deborah Sanders & Anna Piskorz & James Hall & Karen Hosking & Anumithr, 2022. "Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Hongyu Shi & Marc J. Williams & Gryte Satas & Adam C. Weiner & Andrew McPherson & Sohrab P. Shah, 2024. "Allele-specific transcriptional effects of subclonal copy number alterations enable genotype-phenotype mapping in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Adam C. Weiner & Marc J. Williams & Hongyu Shi & Ignacio Vázquez-García & Sohrab Salehi & Nicole Rusk & Samuel Aparicio & Sohrab P. Shah & Andrew McPherson, 2024. "Inferring replication timing and proliferation dynamics from single-cell DNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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