DOI: 10.5281/zenodo.3241399
title: Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival

description: This dataset is related to "Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival" (Cajuso et al.). <strong>Abstract:</strong> 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 find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in <em>APC</em>,<em> </em>likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival. <strong>Sample description: </strong> A signed informed consent was obtained for as many human participants as possible. In cases without a signed informed consent, an authorization from the National Supervisory Authority for Welfare and Health (Dnro 421/04/044/06, Dnro 8048/06.01.03.01/2014, Dnro 358/32/300/05, Dnro 1476/06.01.03.01/2012) was obtained as stated in Finnish law. The study has been reviewed by the Ethics Committee of the Hospital district of Helsinki and Uusima (Dnro 133/E8/03, 408/13/03/03/2009). Permission to use patient information was obtained from the National Institute for Health and Welfare (Dnro 53/07/2000, Dnro THL/1071/5.05.00/2011, Dnro THL/151/5.05.00/2017). <strong>RNA sequencing:</strong> Total RNA from consecutive cryosections was extracted using RNeasy Mini Kit (Qiagen) from 34 tumors that displayed more than 50% of cancer cell percentage (HE staining of cryosections) and RNA integrity&gt;6 (Agilent RNA 6000, Agilent 2100 Bioanalyzer). Paired-end RNA sequencing was performed on the Illumina Hiseq 2000. RNA-seq data was processed using Kallisto (version 0.43.0) software. Kallisto quantification was executed in paired-end mode and aligned against the Ensembl Human reference transcriptome (GRCh37_79). Quantification results from Kallisto were normalized and aggregated to gene-level utilizing sleuth (version 0.28.1) R package with default filtering settings.
description: This work was supported by grants from the Academy of Finland (Finnish Center of Excellence Program 2012-2017, 250345 and 2018-2025, 312041), The Finnish Cancer Society, The European Research Council (268648), The Sigrid Juselius Foundation; Jane and Aatos Erkko Foundation, the Nordic Information for Action eScience Center (NIASC) and Nordic Center of Excellence financed by NordForsk (Project number 62721). We also thank SYSCOL (an EU FP7 Collaborative Project, 258236) for sequencing the RNA samples. The following foundations are acknowledged for personal funding: Ida Montinin Säätio foundation, Cancer Society of Finland, Juhani Ahon Foundation for Medical Research and The Maud Kuistila Memorial Foundation. The authors wish to acknowledge CSC-IT Center for Science, Finland, for computational resources.