1. Cancer-type specific aneuploidies hard-wire chromosome-wide gene expression patterns of their tissue of origin
- Author
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Rachel Adihe Lokanga, Jordi Camps, Annette Lischka, Yuri Lazebnik, Danny Wangsa, Cristina Montagna, Thomas Ried, B. Michael Ghadimi, Daniela Hirsch, Noam Auslander, Yue Hu, Michael J. Difilippantonio, Georg Emons, Darawalee Wangsa, Gert Auer, Jochen Gaedcke, Eytan Ruppin, Daniel Bronder, Sushant Patkar, Markus Brown, Wei Dong Chen, Kerstin Heselmeyer-Haddad, Jens K. Habermann, Marian Grade, and Rüdiger Braun
- Subjects
Genetics ,0303 health sciences ,Cancer type ,Normal tissue ,Chromosome ,Cancer ,Biology ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Gene expression ,medicine ,Carcinogenesis ,Gene ,030304 developmental biology - Abstract
SUMMARYMost carcinomas have characteristic chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is unknown. As aneuploidies directly affect gene expression, we hypothesized that cancer-type specific aneuploidies, which emerge at early stages of tumor evolution, confer adaptive advantages to the physiological requirements of the tissue of origin. To test this hypothesis, we compared chromosomal aneuploidies reported in the TCGA database to chromosome arm-wide gene expression levels of normal tissues from the GTEx database. We find that cancer-type specific chromosomal aneuploidies mirror differential gene expression levels specific to the respective normal tissues which cannot be explained by copy number alterations of resident cancer driver genes. We propose that cancer-type specific aneuploidies “hard-wire” chromosome arm-wide gene expression levels present in normal tissues, favoring clonal expansion and tumorigenesis.One sentence summaryThe clonal evolution of cancer is initiated by tissue-specific transcriptional requirements
- Published
- 2019
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