Chromosomal instability analysis and regional tumor heterogeneity in colon cancer

Chromosomal instability (CIN) is classically defined as an increase in the rate at whichnumerical or structural chromosomal aberrations are acquired in a cancer cell. The number ofsomatic copy number abnormalities (CNAs) revealed by high resolution genomic array can beconsidered as a surrogate marker for CIN, but several points, related to sample processing and dataanalysis, need to be standardized. In this work we analyzed 51 CRC samples and matched normalmucosae by whole genome SNP arrays and compared different bioinformatics tools in order toidentify broad (>25% of a chromosomal arm) and focal somatic copy number abnormalities(BCNAs and FCNAs respectively). In 15 tumors, two samples, separated by at least 1 cm, weretaken from the same tumor mass (double-sampling pairs) in order to evaluate differences indetection of chromosomal abnormalities between distant regions of the same tumor and theirinfluence on CIN quantitative and qualitative analysis. Our data show a high degree of correlationof the quantitative CIN index (somatic BCNA number) between distant tumor regions. On thecontrary, a lower correlation is observed in terms of chromosomal distribution of BCNAs, assummarized by a simplified cytogenetic table. Quantitative or qualitative analysis of FCNAs,including homozygous deletions and high level amplifications, did not add further information onthe CIN status. The use of the index “somatic BCNA number” can be proposed for a robustclassification of tumors as CIN positive or negative even in the presence of a significant tumorregional heterogeneity.