TY - JOUR T1 - Cancer-type specific aneuploidies hard-wire chromosome-wide gene expression patterns of their tissue of origin JF - bioRxiv DO - 10.1101/563858 SP - 563858 AU - Noam Auslander AU - Kerstin Heselmeyer-Haddad AU - Sushant Patkar AU - Daniela Hirsch AU - Jordi Camps AU - Markus Brown AU - Daniel Bronder AU - Wei-Dong Chen AU - Rachel Lokanga AU - Darawalee Wangsa AU - Danny Wangsa AU - Yue Hu AU - Annette Lischka AU - Rüdiger Braun AU - Georg Emons AU - B. Michael Ghadimi AU - Jochen Gaedcke AU - Marian Grade AU - Cristina Montagna AU - Yuri Lazebnik AU - Michael J. Difilippantonio AU - Jens K. Habermann AU - Gert Auer AU - Eytan Ruppin AU - Thomas Ried Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/01/563858.abstract N2 - Most 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 show that cancer-type specific aneuploidies “hard-wire” chromosome arm-wide gene expression levels present in normal tissues and propose that the clonal evolution of cancer is initiated by tissue-specific transcriptional requirements. ER -