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Intra-tumor Genetic Heterogeneity in Rectal Canger

ABSTRACT: Colorectal cancer arises in part from the cumulative effects of multiple gene lesions. Recent studies in selected cancer types have revealed significant intra-tumor genetic heterogeneity and highlighted its potential role in disease progression and resistance to therapy. We hypothesized the existence of significant intra-tumor genetic heterogeneity in rectal cancers involving variations in localized somatic mutations and copy number abnormalities. Two or three spatially disparate areas from each of six rectal tumors were dissected and subjected to next-generation whole exome DNA sequencing, Oncoscan SNP arrays, and targeted confirmatory sequencing and analysis. The resulting data were integrated to define subclones using SciClone. Mutant-allele tumor heterogeneity (MATH) scores, mutant allele frequency correlation, and mutation percent concordance were calculated, and Copy number analysis including measurement of correlation between samples was performed.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73365 | GEO | 2015/09/24

SECONDARY ACCESSION(S): PRJNA296805

REPOSITORIES: GEO

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Intra-tumor Genetic Heterogeneity in Rectal Canger

Project description:Colorectal cancer arises in part from the cumulative effects of multiple gene lesions. Recent studies in selected cancer types have revealed significant intra-tumor genetic heterogeneity and highlighted its potential role in disease progression and resistance to therapy. We hypothesized the existence of significant intra-tumor genetic heterogeneity in rectal cancers involving variations in localized somatic mutations and copy number abnormalities. Two or three spatially disparate areas from each of six rectal tumors were dissected and subjected to next-generation whole exome DNA sequencing, Oncoscan SNP arrays, and targeted confirmatory sequencing and analysis. The resulting data were integrated to define subclones using SciClone. Mutant-allele tumor heterogeneity (MATH) scores, mutant allele frequency correlation, and mutation percent concordance were calculated, and Copy number analysis including measurement of correlation between samples was performed. Affymetrix OncoScan V3 arrays were run on all tumor samples. The OncoScan array platform consists of a set of 217k probes designed specifically for profiling tumors. The overall resolution of the assay for detecting copy number change generates data at 50-100kb resolution across a set of 891 cancer genes, and 300-400kb across the rest of the genome. Raw array florescence intensity data generated on the Affymetrix scanners in the form of CEL files were loaded into the OncoScan Console software v.1.1.0 (Affymetrix, Santa Clara, California). Quality control statistics as well as integrated OSCHP files were generated by OncoScan Console. The standard Affymetrix reference control file for OncoScan data was used for processing the arrays.

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