Druliner BR et al. -Defects in APC and WNT signaling are associated with chromosome instability (CIN) in hereditary CRC, but the genetic causes for CIN in sporadic CRC are unknown.Based on the current study, patients with sporadic CRC were shown to have genetic aberrations enriched on 18q in blood, normal colon epithelium, and non-malignant polyp lesions. Indeed, the genetic aberrations may be useful as clinical markers for sporadic CRC detection and risk assessment.

Methods

• High-density SNP array and exome data from The Cancer Genome Atlas were used to characterize loss of heterozygosity (LOH) and copy number variation (CNV) in the peripheral blood, and normal colon and corresponding tumor tissues in 15 CRC patients with proficient mismatch repair (MMR) and 24 CRC patients with deficient MMR.

Results

• A high frequency of 18q LOH was demonstrated in tumors and arm-specific enrichment of genetic aberrations on 18q in the normal colon and blood.
• The genetic aberrations were specific to the sporadic, pMMR CRC.
• Although tumor sample genetic aberrations were shown for genes commonly mutated in hereditary CRC, such as APC, CTNNB1, SMAD4, and BRAF, none of the mutated genes exhibited LOH or CNV in the normal colon or blood.
• DCC located on 18q21.1 were shown to be the most common genes with genetic aberrations in the tumor.
• In an independent cohort of 13 patients subjected to Whole Genome Sequencing, LOH and CNV were shown on 18q in adenomatous polyp and tumor tissues.