Applied Tumor Genomics Research Program, Faculty of Medicine University of Helsinki, Biomedicum Helsinki, PO Box 63, (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63, (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Nat Commun. 2019 Sep 6;10(1):4022. doi: 10.1038/s41467-019-11770-0.
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.
结直肠癌（CRC）中的基因组不稳定性途径已得到广泛研究，但逆转录转座子在结直肠肿瘤发生中的作用仍知之甚少。虽然逆转座子通常受到抑制，但它们在几种人类癌症中变得活跃，特别是胃肠道癌症。在这里，我们对 202 个结直肠肿瘤全基因组中的逆转座子插入进行了表征，并研究了它们与分子和临床特征的关联。我们发现肿瘤之间的逆转座子活性变化很大，并在 15 个已知的癌症基因中鉴定出了复发性插入。在大约 1%的情况下，我们在 APC 中发现了插入，可能是肿瘤起始事件。插入与 CpG 岛甲基化表型和等位基因失衡的基因组分数呈正相关。在临床上，高数量的插入与较差的疾病特异性生存独立相关。
