An analysis of substitution, deletion and insertion mutations in cancer genes

Iengar, Prathima (2012) An analysis of substitution, deletion and insertion mutations in cancer genes. In: NUCLEIC ACIDS RESEARCH, 40 (14). pp. 6401-6413.

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Abstract

Cancer-associated mutations in cancer genes constitute a diverse set of mutations associated with the disease. To gain insight into features of the set, substitution, deletion and insertion mutations were analysed at the nucleotide level, from the COSMIC database. The most frequent substitutions were c -> t, g -> a, g -> t, and the most frequent codon changes were to termination codons. Deletions more than insertions, FS (frameshift) indels more than I-F (in-frame) ones, and single-nucleotide indels, were frequent. FS indels cause loss of significant fractions of proteins. The 5'-cut in FS deletions, and 5'-ligation in FS insertions, often occur between pairs of identical bases. Interestingly, the cut-site and 3'-ligation in insertions, and 3'-cut and join-pair in deletions, were each found to be the same significantly often (p < 0.001). It is suggested that these features aid the incorporation of indel mutations. Tumor suppressors undergo larger numbers of mutations, especially disruptive ones, over the entire protein length, to inactivate two alleles. Proto-oncogenes undergo fewer, less-disruptive mutations, in selected protein regions, to activate a single allele. Finally, catalogues, in ranked order, of genes mutated in each cancer, and cancers in which each gene is mutated, were created. The study highlights the nucleotide level preferences and disruptive nature of cancer mutations.

Item Type:	Journal Article
Publication:	NUCLEIC ACIDS RESEARCH
Publisher:	OXFORD UNIV PRESS
Additional Information:	Copy right for this article belongs to Oxford University Press, England
Keywords:	SOMATIC MUTATIONS;MISSENSE MUTATIONS;FUNCTIONAL IMPACT; PROTEIN-KINASES;DNA;FREQUENCY;DISEASE;GENOMES;CELLS;CPG
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	15 Oct 2012 05:09
Last Modified:	15 Oct 2012 05:09
URI:	http://eprints.iisc.ac.in/id/eprint/45098

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