CpG/CpNpG motifs in the coding region are preferred sites for mutagenesis in the breast cancer susceptibility genes

Lydia W.T. Cheung, Yiu Fai Lee, Tuen Wai Ng, Wai Ki Ching, Ui Soon Khoo, Kwok Po NG, Alice S.T. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The range of BRCA1/BRCA2 gene mutations is diverse and the mechanism accounting for this heterogeneity is obscure. To gain insight into the endogenous mutational mechanisms involved, we evaluated the association of specific sequences (i.e. CpG/CpNpG motifs, homonucleotides, short repeats) and mutations within the genes. We classified 1337 published mutations in BRCA1 (1765 BRCA2 mutations) for each specific sequence, and employed computer simulation combined with mathematical calculations to estimate the true underlying tendency of mutation occurrence. Interestingly, we found no mutational bias to homonucleotides and repeats in deletions/insertions and substitutions but striking bias to CpG/CpNpG in substitutions in both genes. This suggests that methylation-dependent DNA alterations would be a major mechanism for mutagenesis.

Original languageEnglish
Pages (from-to)4668-4674
Number of pages7
JournalFEBS Letters
Volume581
Issue number24
DOIs
Publication statusPublished - 2 Oct 2007

Scopus Subject Areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

User-Defined Keywords

  • BRCA1
  • BRCA2
  • Breast cancer susceptibility gene
  • Gene mutation

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