Elevated incidence of somatic mutations at prevalent genetic sites
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Article number | bbae065 |
Journal / Publication | Briefings in Bioinformatics |
Volume | 25 |
Issue number | 2 |
Online published | 28 Feb 2024 |
Publication status | Published - Mar 2024 |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85186363377&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(8d355617-7ca2-46ce-923f-e3ce098da8bd).html |
Abstract
The common loci represent a distinct set of the human genome sites that harbor genetic variants found in at least 1% of the population. Small somatic mutations occur at the common loci and non-common loci, i.e. csmVariants and ncsmVariants, are presumed with similar probabilities. However, our work revealed that within the coding region, common loci constituted only 1.03% of all loci, yet they accounted for 5.14% of TCGA somatic mutations. Furthermore, the small somatic mutation incidence rate at these common loci was 2.7 times that observed in the non-common. Notably, the csmVariants exhibited an impressive recurrent rate of 36.14%, which was 2.59 times of the ncsmVariants. The C-to-T transition at the CpG sites accounted for 32.41% of the csmVariants, which was 2.93 times for the ncsmVariants. Interestingly, the aging-related mutational signature contributed to 13.87% of the csmVariants, 5.5 times that of ncsmVariants. Moreover, 35.93% of the csmVariants contexts exhibited palindromic features, outperforming ncsmVariant contexts by 1.84 times. Notably, cancer patients with higher csmVariants rates had better progression-free survival. Furthermore, cancer patients with high-frequency csmVariants enriched with mismatch repair deficiency were also associated with better progression-free survival. The accumulation of csmVariants during cancerogenesis is a complex process influenced by various factors. These include the presence of a substantial percentage of palindromic sequences at csmVariants sites, the impact of aging and DNA mismatch repair deficiency. Together, these factors contribute to the higher somatic mutation incidence rates of common loci and the overall accumulation of csmVariants in cancer development. © The Author(s) 2024. Published by Oxford University Press.
Research Area(s)
- aging, common loci, mutation incidence, TCGA somatic mutations
Citation Format(s)
Elevated incidence of somatic mutations at prevalent genetic sites. / Wang, Mengyao; Li, Shuai Cheng; Shen, Bairong.
In: Briefings in Bioinformatics, Vol. 25, No. 2, bbae065, 03.2024.
In: Briefings in Bioinformatics, Vol. 25, No. 2, bbae065, 03.2024.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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