Genetic profiling of metastatic colorectal cancer

The genetics of metastatic colorectal cancer has been studied for many years using a variety of techniques with limited resolutions, which hampers the identification of specific underlying cancer-associated genes. The introduction of high-density single nucleotide polymorphism (SNP) arrays has allowed the identification of small regions of chromosomal gains and losses with a resolution down to 2.5 kb. Here we used 500K SNP mapping arrays to map the overall genetic lesions present at diagnosis in 23 primary sporadic CRC patients with liver metastases. In order to evaluate the consistency of the chromosomal changes identified by the SNP-arrays, interphase FISH analysis was performed in parallel for a total of 24 chromosome regions from 20 different chromosomes. The highest frequency of copy number (CN) losses detected corresponded to chromosomes 1p (n = 17; 74%), 8p (n = 18; 78%), 14q (n = 15; 65%), 17p (n = 19; 83%), 18 (n = 21; 91%), and 22q (n = 17; 74%), while CN gains more frequently involved chromosomes 1q (n = 10; 43%), 7 (n = 20; 87%), 8q (n = 17; 74%), 13q (n = 18; 78%), 20q (n = 20; 87%), and X (n = 13; 57%). SNP arrays allowed the identification of small (<1.3 Mb) and extensive/large (>1.5 Mb) DNA alterations. Interestingly, several of these regions contain cancer genes known to be involved in colorectal cancer and metastatic processes (particularly among the amplified chromosome regions). Overall our results showed a high degree of correlation between both methods, including the most frequently altered regions. Moreover, four recurrent chromosomal breakpoints were identified, at chromosomes 1p12, 8p12, 17p11.2, and 20p12.1. Interestingly, detailed analysis of recurrent chromosomal breakpoints revealed a highly prevalent breakpoint at 17p11.2, which may target genes such as FAM27, whose role in the disease deserves further investigation.