Whole-genome reconstruction and mutational signatures in gastric cancer – Genome Biol.
Genome Biol. 2012 Dec 13;13(12):R115.
Whole-genome reconstruction and mutational signatures in gastric cancer. Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques PE, Teo AS, Cutcutache I, Zhang Z, Lee WH, Sia YY, Gao S, Ariyaratne PN, Ho A, Woo XY, Veeravali L, Ong CK, Deng N, Desai KV, Khor CC, Hibberd ML, Shahab A, Rao J, Wu M, Teh M, Zhu F, Chin SY, Pang B, So JB, Bourque G, Soong R, Sung WK, Tean Teh B, Rozen S, Ruan X, Yeoh KG, Tan PB, Ruan Y.
http://www.ncbi.nlm.nih.gov/pubmed/23237666
Some thoughts, much from WC:
Looks like the data is freely available via GEO ID : GSE30833 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30833
The article by Nagarajan et al. highlights the authors efforts to utilize de novo genome assembly of gastric cancer genomes to detect not only single nucleotide variants (SNV’s) and short
insertions/deletions (indels), but also larger scale genomic structural variation (SV) that could be signatures of cancer genomes. It is to be applauded that this is a whole genome analysis.
The authors present several interesting findings such as enrichment for C->A and T->A mutations in both cancer genomes, enrichment for C->A and C->T mutations in the H. pylori infected cancer genome (evidence of cytosine specific transcription mediated DNA repair due to deamination), and amplification and deletion of regions on chromosome 12 in the non-H. pylori infected genome.
Although copy number variants (CNV) could potentially be detected by exome sequencing alone, whole genome sequence enables the precise localization of such events, as well as the detection of variation in non-coding regions.
Their methodology relies on combining high-throughput short-read sequencing with longer DNA-PET (paired end tags) in order to construct higher confidence de novo assemblies with longer contiguous regions.