A distinct tumor suppressor gene locus on chromosome 15q21.1 in sporadic form of colorectal cancer.

The SM1311 family is an Ashkenazi family with dominantly inherited predisposition to colorectal adenomas and carcinomas and has a high-penetrance locus in chromosome 15q, with a multipoint logarithm of the odds score of 3.06 at marker D15S118. In the present study, we performed a high-density loss of heterozygosity study with 13 polymorphic microsatellite markers, including D15S118, spanning 15q15.3-q22.1, on 70 cases of the sporadic form of colorectal tumors. Our deletion mapping data showed a locus at D15S968 in chromosomal sub-band 15q21.1 may harbor a tumor suppressor gene in an area <0.521 Mb in physical map distance defined by markers D15S514 and D15S222. THBS1, 0.185 Mb proximal to D15S968, is the nearest known gene to this specific narrow loss of heterozygosity region. Thus, we speculate that THBS1 might be the most probable candidate gene involved in colorectal cancer carcinogenesis.