Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival

Tatiana Cajuso, Päivi Sulo, Tomas Tanskanen, Riku Katainen, Aurora Taira, Ulrika A. Hänninen, Johanna Kondelin, Linda Forström, Niko Välimäki, Mervi Aavikko, Eevi Kaasinen, Ari Ristimäki, Selja Koskensalo, Anna Lepistö, Laura Renkonen-Sinisalo, Toni Seppälä, Teijo Kuopio, Jan Böhm, Jukka-Pekka Mecklin, Outi Kilpivaara, Esa Pitkänen, Kimmo Palin, and Lauri A. Aaltonen

Nov 05, 2018

Received Date: 23rd July 18

Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We found highly variable retrotransposon activity among tumors and identified recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identified insertions in APC, likely to be tumor-initiating events. Insertions were positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions was independently associated with poor disease-specific survival.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature