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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dai
Yuan-Chang
YC
Department of Pathology, National Cheng Kung University Hospital, 138 Sheng-Li Road, 704 Tainan, Taiwan.
Ho
Chung-Liang
CL
Tsai
Yi-Chang
YC
Hsu
Yung-Hsiang
YH
Chang
Yu-Chuang
YC
Liu
Hsiao-Sheng
HS
Chen
Helen Hai-Wen
HH
Chow
Nan-Haw
NH
D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D003138:Common Bile Duct Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*