Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
Cajuso, T., Sulo, P., Tanskanen, T., Katainen, R., Taira, A., Hänninen, U. A., Kondelin, J., Forsström, L., Välimäki, N., Aavikko, M., Kaasinen, E., Ristimäki, A., Koskensalo, S., Lepistö, A., Renkonen-Sinisalo, L., Seppälä, T., Kuopio, T., Böhm, J., Mecklin, J.-P., . . . Aaltonen, L. A. (2019). Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival. Nature Communications, 10, Article 4022. https://doi.org/10.1038/s41467-019-11770-0
Julkaistu sarjassa
Nature CommunicationsTekijät
Päivämäärä
2019Tekijänoikeudet
© The Authors 2019
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 APC, 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.
Julkaisija
Nature Publishing GroupISSN Hae Julkaisufoorumista
2041-1723Asiasanat
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https://converis.jyu.fi/converis/portal/detail/Publication/32781740
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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. ...Lisenssi
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