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KMID : 0620920210530030446
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Experimental & Molecular Medicine
2021 Volume.53 No. 3 p.446 ~ p.456
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High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer
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Kim Jeong-Eun
Choi Jae-Yong
Sung Chang-Ohk
Hong Yong-Sang
Kim Sun-Young
Lee Hyun-Jung
Kim Tae-Won
Kim Jong-Il
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Abstract
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The global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P?=?0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.
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KEYWORD
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Colon cancer, Medical genomics
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