Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17�cM interval

Abstract

The genetic basis for gastrointestinal and ampullary carcinomas remains uncertain. This study was performed to pinpoint novel chromosomal region involved in the tumorigenesis of gastrointestinal tract. We screened the allelic status on 16 chromosomal arms in a patient with synchronous ampullary carcinoma and gastric cancer, but who had no family history of familial cancer syndrome. The significance of the shared 14q deletion was examined on clinical cohorts of sporadic gastric (n=12) and ampullary (n=10) carcinoma, respectively. Then, high-density allelotype mapping was performed on 14q32 by using 23 microsatellite markers for the synchronous tumors. The synchronous gastric and ampullary carcinomas had no frameshift mutations in the APC, MSH2, MSH3, and MSH6 genes. Among the microsatellite markers screened, only D14S267 showed identical loss in the synchronous tumors. The same allelic loss was also detected in one of ampullary carcinomas (10%) and two of gastric cancers (16.7%). Fine mapping of 14q determined a minimally deleted region between D14S65 and D14S1010 (17 centiMorgans) for the synchronous tumors. This study illustrates a paradigm using molecular genetic approach in identifying chromosome 14q32 that may harbor a tumor suppressor gene involved in the pathogenesis of a subset of gastrointestinal and ampullary malignancies.