Clinical Significance of Loss of Heterozygosity on Chromosome 14q in Sporadic Colorectal Carcinomas

ABSTRACT

PURPOSE AND METHODS: Colorectal carcinogenesis is a process with multiple steps involving proto- oncogenes, tumor suppressive genes, and mutator genes. Losses of heterozygosity (LOH) on APC, DCC, and TP53 loci are well known chromosomal changes for the inactivation of tumor suppressive genes. Additionally, LOH in colorectal carcinomas (CRC) are frequently found at other loci, including 1p, 8p, 11q, 14q, and 22q. LOH on 14q are quite frequent in bladder, ovarian, renal-cell carcinomas, as well as other types of carcinomas. Previous studies on CRC showed overall rate of LOH on chromosome 14q to be high, the smallest region of overlap of deletion was located at the distal portion of 14q, and a higher rate of LOH was found in more advanced tumors. To investigate whether LOH on chromosome 14q is confined to the distal part or whether it is related with prognosis, we performed an LOH study with 6 microsatellite markers covering the entire arm of 14q in 77 sporadic colorectal cancers and compared it with clinical parameters. RESULTS: Thirty-six (36) tumors (46.7%) showed LOH at one or more markers, and the highest rate was observed in D14S48 (43.5%) and the lowest in D14S297 (30.6%). No statistical differences were seen at different loci of 14q. We observed LOH in 17 less- advanced tumors (Dukes' A & B) and in 19 advanced tumors (Dukes' C & D). There is little evidence that LOH of 14q is related to tumor recurrence, the disease-free survival rate, or the overall survival. CONCLUSION: These results indicate that the entire long arm of chromosome 14 may delete in sporadic colorectal cancers but this loss may not be related to tumor stage and prognosis. We provide evidence that one or more tumor suppressive loci on chromosome 14q may contribute to colorectal carcinogenesis.