Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma
Abstract Background Non-synonymous mutations altering tumor suppressor genes and oncogenes are widely studied. However, synonymous mutations, which do not alter the protein sequence, are rarely investigated in melanoma genome studies. Methods We explored the role of somatic synonymous mutations in m...
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doaj-b3d82cf8fe644b1ab93cd842237ba1ba2021-04-02T09:52:39ZengBMCBMC Medical Genomics1755-87942020-04-0113S511010.1186/s12920-020-0685-2Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanomaDi Zhang0Junfeng Xia1College of information science and engineering, Shaoguan UniversityInstitutes of Physical Science and Information Technology, Anhui UniversityAbstract Background Non-synonymous mutations altering tumor suppressor genes and oncogenes are widely studied. However, synonymous mutations, which do not alter the protein sequence, are rarely investigated in melanoma genome studies. Methods We explored the role of somatic synonymous mutations in melanoma samples from TCGA (The Cancer Genome Atlas). The pathogenic synonymous mutation and neutral synonymous mutation data were used to assess the significance of pathogenic synonymous mutations in melanoma likely to affect genetic regulatory elements using Fisher’s exact test. Poisson distribution probabilities of each gene were used to mine the genes with multiple potential functional synonymous mutations affecting regulatory elements. Results Concentrating on five types of genetic regulatory functions, we found that the mutational patterns of pathogenic synonymous mutations are mostly involved in exonic splicing regulators in near-splicing sites or inside DNase I hypersensitivity sites or non-optimal codon. Moreover, the sites of miRNA binding alteration exhibit a significantly lower rate of evolution than other sites. Finally, 12 genes were hit by recurrent potentially functional synonymous mutations, which showed statistical significance in the pathogenic mutations. Among them, nine genes (DNAH5, ADCY8, GRIN2A, KSR2, TECTA, RIMS2, XKR6, MYH1, SCN10A) have been reported to be mutated in melanoma, and other three genes (SLC9A2, CASR, SLC8A3) have a great potential to impact melanoma. Conclusion These findings confirm the functional consequences of somatic synonymous mutations in melanoma, emphasizing the significance of research in future studies.http://link.springer.com/article/10.1186/s12920-020-0685-2MelanomaSynonymous mutationsRegulatory elements |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Di Zhang Junfeng Xia |
spellingShingle |
Di Zhang Junfeng Xia Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma BMC Medical Genomics Melanoma Synonymous mutations Regulatory elements |
author_facet |
Di Zhang Junfeng Xia |
author_sort |
Di Zhang |
title |
Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma |
title_short |
Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma |
title_full |
Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma |
title_fullStr |
Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma |
title_full_unstemmed |
Somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma |
title_sort |
somatic synonymous mutations in regulatory elements contribute to the genetic aetiology of melanoma |
publisher |
BMC |
series |
BMC Medical Genomics |
issn |
1755-8794 |
publishDate |
2020-04-01 |
description |
Abstract Background Non-synonymous mutations altering tumor suppressor genes and oncogenes are widely studied. However, synonymous mutations, which do not alter the protein sequence, are rarely investigated in melanoma genome studies. Methods We explored the role of somatic synonymous mutations in melanoma samples from TCGA (The Cancer Genome Atlas). The pathogenic synonymous mutation and neutral synonymous mutation data were used to assess the significance of pathogenic synonymous mutations in melanoma likely to affect genetic regulatory elements using Fisher’s exact test. Poisson distribution probabilities of each gene were used to mine the genes with multiple potential functional synonymous mutations affecting regulatory elements. Results Concentrating on five types of genetic regulatory functions, we found that the mutational patterns of pathogenic synonymous mutations are mostly involved in exonic splicing regulators in near-splicing sites or inside DNase I hypersensitivity sites or non-optimal codon. Moreover, the sites of miRNA binding alteration exhibit a significantly lower rate of evolution than other sites. Finally, 12 genes were hit by recurrent potentially functional synonymous mutations, which showed statistical significance in the pathogenic mutations. Among them, nine genes (DNAH5, ADCY8, GRIN2A, KSR2, TECTA, RIMS2, XKR6, MYH1, SCN10A) have been reported to be mutated in melanoma, and other three genes (SLC9A2, CASR, SLC8A3) have a great potential to impact melanoma. Conclusion These findings confirm the functional consequences of somatic synonymous mutations in melanoma, emphasizing the significance of research in future studies. |
topic |
Melanoma Synonymous mutations Regulatory elements |
url |
http://link.springer.com/article/10.1186/s12920-020-0685-2 |
work_keys_str_mv |
AT dizhang somaticsynonymousmutationsinregulatoryelementscontributetothegeneticaetiologyofmelanoma AT junfengxia somaticsynonymousmutationsinregulatoryelementscontributetothegeneticaetiologyofmelanoma |
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1724168466846449664 |