Abstract
Purpose
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.
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References
Bando T, Kato Y, Ihara Y, Yamagishi F, Tsukada K, Isobe M (1999) Loss of heterozygosity of 14q32 in colorectal carcinoma. Cancer Genet Cytogenet 111:161–165
Chang YC, Ho CL, Chen HW, Chang TT, Lai WW, Dai YC, Lee WY, Chow NH (2002) Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum. Br J Cancer 87:1449–1453
Chen KS, Lai MK, Huang CC, Chu SH, Leu ML (1995) Urologic cancers in uremic patients. Am J Kid Dis 25:694–700
Eisenberger CF, Schoenberg M, Enger C, Hortopan S, Shah S, Chow NH, Marshall FF, Sidransky D (1999) Diagnosis of renal cancer by molecular urinalysis. J Natl Cancer Inst 91:2028–2032
Fishel R, Lescoe MK, Rao MRS, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038
Hidaka E, Yanagisawa A, Seki M, Setoguchi T, Kato Y (2001) Genetic alterations and growth pattern in biliary duct carcinomas: loss of heterozygosity at chromosome 5q bears a close relation with polypoid growth. Gut 48:656–659
Horii A, Han H-J, Shimada M, Yanagisawa A, Kato Y, Ohta H, Yasui W, Tahara E, Nakamura Y (1994) Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. Cancer Res 54:3373–3375
Ihara Y, Kato Y, Bando T, Yamagishi F, Minamimura T, Sakamoto T, Tsukada K, Isobe M (2002) Allelic imbalance of 14q32 in esophageal carcinoma. Cancer Genet Cytogenet 135:177–181
Kang YK, Kim YI, Kim WH (2000) Allelotype analysis of intrahepatic cholangiocarcinoma. Mod Pathol 13:627–631
Kim YH, Kim NG, Lim JG, Park C, Kim H (2001) Chromosomal alterations in paired gastric adenomas and carcinomas. Am J Pathol 158:655–662
Kitano S, Morotomi I, Oiwa T, Hirose S, Minoda S, Yamaguchi K, Sakato K (1984) Simultaneous early carcinomas of the ampulla of Vater and the stomach. Report of a case involving chronic inactive hepatitis. S Afr Med J 66:656–658
Nagy A, Chudek J, Kovacs G (2001) Accumulation of allelic changes at chromosomes 7p, 18q, and 2 in parathyroid lesions of uremic patients. Lab Invest 81:527–533
Neugut AI, Robinson E (1992) Multiple primary neoplasms. Cancer J 5:245–248
Nishizuka S, Tamura G, Terashima M, Satodate R (1998) Loss of heterozygosity during the development and progression of differentiated adenocarcinoma of the stomach. J Pathol 185:38–43
Ohtani H, Yashiro M, Onoda N, Nishioka N, Kato Y, Yamamoto S, Fukushima S, Hirakawa YS, Chung K (2000) Synchronous multiple primary gastrointestinal cancer exhibits frequent microsatellite instability. Int J Cancer 86:678–683
Renault PF, Hillemand B, Anagnostides JC, Meyer M, Toulemonde P (1978) Congenital cyst of the common hepatic duct. Adenocarcinoma of the gall bladder and of the stomach. J Chir (Paris) 115:623–626
Rosenberg C, Geelen E, Jszenga MJ, Pearson P, Tanke HJ, Dinjens WN, van Dekken H (2002) Spectrum of genetic changes in gastro-esophageal cancer cell lines determined by an integrated molecular cytogenetic approach. Cancer Genet Cytogenet 135:35–41
Schlossberg D, Weber W, Stoffel U, Henggeler K, Stocker H, Foeppl M, Akovbiantz A (1988) Periampullary, colorectal and gastric cancer in two siblings. Int J Cancer 42:839–841
Shimada M, Horii A, Sasaki S, Yanagisawa A, Kato Y, Yamashita K, Okagawa K, Yamasaki K, Ishiguro S, Inoue M, Shiozaki H, Nakamura Y (1995) Infrequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers of the esophagus and various other tissues. Jpn J Cancer Res 86:511–515
Shiraishi K, Kusano N, Okita S, Oga A, Okita K, Sasaki K (1999) Genetic aberrations detected by comparative genomic hybridization in biliary tract cancers. Oncology 57:42–49
Shiraishi K, Okita K, Kusano N, Harada T, Kondoh S, Okita S, Ryozawa S, Ohmura R, Noguchi T, Iida Y, Akiyama T, Oga A, Fukumoto Y, Furuya T, Kawauchi S, Sasaki K (2001) A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas. Oncology 60:151–161
Takayasu K, Kasugai H, Ikeya S, Muramatsu Y, Moriyama N, Makuuchi M, Yamazaki S, Hirohashi S (1992) A clinical and radiologic study of primary liver cancer associated with extrahepatic primary cancer. Cancer 69:45–51
van Dekken H, Geelen E, Dinjens WN, Wijnhoven BP, Tilanus HW, Tanke HJ, Rosenberg C (1999) Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31–32.1 discriminates between esophageal (Barrett’s) and gastric cardia adenocarcinomas. Cancer Res 59:748–752
Yanagi M, Keller G, Mueller J, Walch A, Werner M, Stein HJ, Siewert JR, Hofler H (2000) Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach. Virchows Arch 437:605–610
Zhou XP, Hoang J-M, Li YJ, Seruca R, Carneiro F, Sobrinho-Simoes M, Lothe RA, Gleeson CM, Russell SEH, Muzeau F, Fléjou J-F, Hoang-Xuan K, Lidereau R, Thomas G, Richard Hamelin R (1998) Determination of the replication error phenotype in human tumors without the requirement for matching normal DNA by analysis of mononucleotide repeat microsatellites. Genes Chromosomes Cancer 21:101–107
Acknowledgement
This study was supported by research grants NSC91-2320-B-006-056 & NSC91-2321-B-006-003 from the National Science Council, and 91-B-FA09-1-4 from the Ministry of Education (MOE Program for Promoting Academic Excellent of Universities), Taiwan
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The doctors Dai YC and Ho CL contributed equally to this study.
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Dai, YC., Ho, CL., Tsai, YC. et al. Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17 cM interval. J Cancer Res Clin Oncol 131, 94–100 (2005). https://doi.org/10.1007/s00432-004-0622-3
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DOI: https://doi.org/10.1007/s00432-004-0622-3