Novel genomic technologies and molecular diagnostics in Colorectal Cancer

Cancer is a disease of the genome that is characterized by substantial variability in the clinical course and response to therapies. Colorectal cancer (CRC) is a heterogeneous cancer and represents an ideal model to investigate and elucidate the genetic alterations involved in tumor onset and progression. In this study 51 CRC patients were subdivided into groups according to the presence of microsatellite instability (MSI) and chromosomal instability (CIN). Of the 51 CRCs, 13.73% were MSI and 86.27% were microsatellite stable (MSS). The frequency of KRAS mutations in MSI-H and in MSS cancer was 28.57% and 40.91%, respectively. To identify and characterize genomic alteration associated with colorectal cancer (CRC) the samples were analyzed with the last generation of Affymetrix single nucleotide polymorphism/CNV microarrays (SNP Array 6.0) and two new tools were implemented, Broad Cytogenetic Analysis (BroCyA) and Focal Cytogenetic Analysis (FoCyA), to identify broad (> ¼ chromosomal arm) and focal aberrations (< ¼ chromosomal arm). Broad copy number gains were noted on chromosomes 7, 8q, 9, 13q, 17q, 20 and broad copy number losses on chromosomes 4, 5q, 8p, 17p, 18, 19p, 20p and 22q. Moreover recurrent high level amplifications (HLAs) (copy number > 5.2) were located on chromosome 20, in regions containing known cancer pathway genes as STK4 and ID1, and homozygous deletions (HoD) containing potential new candidate tumor, suppressors such as BTG4 and D4S234E were located on chromosomes 11 and 4. Recurrent somatic focal events (gains and losses) were identified in regions encompassing potential new candidate tumor suppressors and oncogenes, such as A2BP1 and PRDM16 Finally, several copy neutral-loss of heterozygosities (CN-LOHs) were detected, more frequently on chromosome 7p and 22q. In conclusion, in this study some novel broad and focal copy number abnormalities (CNAs) and CN-LOHs were revealed in CRC. The precise and large-scale measurement of CNAs and CN-LOHs in the CRC genome provides a list of genes that might be involved in cancer development.