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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1999 Jul;52(7):504–508. doi: 10.1136/jcp.52.7.504

Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability.

D C Fang 1, J R Jass 1, D X Wang 1, X D Zhou 1, Y H Luo 1, J Young 1
PMCID: PMC501490  PMID: 10605402

Abstract

AIM: To investigate the role of DNA microsatellite instability (MSI) in gastric carcinogenesis by studying associations between MSI status, clinicopathological features, and loss of genetic loci. METHODS: Six microsatellite loci and loss of heterozygosity at APC, DCC, and MCC were analysed by polymerase chain reaction based methods in 53 cases of advanced gastric cancer. RESULTS: MSI was observed in 32.1% of gastric carcinomas (17/53) and 20% of foci of intestinal metaplasia (3/15). Seven gastric carcinomas (13.7%) were MSI-high (MSI-H) (three loci or more) and 10 (18.9%) were MSI-low (MSI-L) (one or two loci). The frequency of MSI-H was higher in intestinal (25.0%) than in diffuse carcinomas (3.7%) (p < 0.05). None of the MSI-H tumours showed loss of heterozygosity at APC, MCC, or DCC loci. CONCLUSIONS: MSI may have an important and early role in a subset of gastric cancers, particularly the intestinal type. The MSI-H subset of gastric cancer has features in common with its colorectal counterpart, whereas MSI-L and microsatellite stable cancers appear to develop through the loss of heterozygosity pathway.

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  1. Boland C. R., Thibodeau S. N., Hamilton S. R., Sidransky D., Eshleman J. R., Burt R. W., Meltzer S. J., Rodriguez-Bigas M. A., Fodde R., Ranzani G. N. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998 Nov 15;58(22):5248–5257. [PubMed] [Google Scholar]
  2. Buonsanti G., Calistri D., Padovan L., Luinetti O., Fiocca R., Solcia E., Ranzani G. N. Microsatellite instability in intestinal- and diffuse-type gastric carcinoma. J Pathol. 1997 Jun;182(2):167–173. doi: 10.1002/(SICI)1096-9896(199706)182:2<167::AID-PATH830>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  3. Chong J. M., Fukayama M., Hayashi Y., Takizawa T., Koike M., Konishi M., Kikuchi-Yanoshita R., Miyaki M. Microsatellite instability in the progression of gastric carcinoma. Cancer Res. 1994 Sep 1;54(17):4595–4597. [PubMed] [Google Scholar]
  4. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992 Dec 15;52(24):6735–6740. [PubMed] [Google Scholar]
  5. Dietmaier W., Wallinger S., Bocker T., Kullmann F., Fishel R., Rüschoff J. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res. 1997 Nov 1;57(21):4749–4756. [PubMed] [Google Scholar]
  6. Fujimoto S., Takahashi M., Ohkubo H., Mutou T., Kure M., Masaoka H., Kobayashi K. Comparative clinicopathologic features of early gastric cancer in young and older patients. Surgery. 1994 Apr;115(4):516–520. [PubMed] [Google Scholar]
  7. Gao X., Honn K. V., Grignon D., Sakr W., Chen Y. Q. Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinomas. Cancer Res. 1993 Jun 15;53(12):2723–2727. [PubMed] [Google Scholar]
  8. Gleeson C. M., Sloan J. M., McGuigan J. A., Ritchie A. J., Weber J. L., Russell S. E. Widespread microsatellite instability occurs infrequently in adenocarcinoma of the gastric cardia. Oncogene. 1996 Apr 18;12(8):1653–1662. [PubMed] [Google Scholar]
  9. Han H. J., Yanagisawa A., Kato Y., Park J. G., Nakamura Y. Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res. 1993 Nov 1;53(21):5087–5089. [PubMed] [Google Scholar]
  10. Hayden J. D., Cawkwell L., Sue-Ling H., Johnston D., Dixon M. F., Quirke P., Martin I. G. Assessment of microsatellite alterations in young patients with gastric adenocarcinoma. Cancer. 1997 Feb 15;79(4):684–687. doi: 10.1002/(sici)1097-0142(19970215)79:4<684::aid-cncr4>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  11. Hayden J. D., Martin I. G., Cawkwell L., Quirke P. The role of microsatellite instability in gastric carcinoma. Gut. 1998 Feb;42(2):300–303. doi: 10.1136/gut.42.2.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ionov Y., Peinado M. A., Malkhosyan S., Shibata D., Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993 Jun 10;363(6429):558–561. doi: 10.1038/363558a0. [DOI] [PubMed] [Google Scholar]
  13. Jass J. R., Do K. A., Simms L. A., Iino H., Wynter C., Pillay S. P., Searle J., Radford-Smith G., Young J., Leggett B. Morphology of sporadic colorectal cancer with DNA replication errors. Gut. 1998 May;42(5):673–679. doi: 10.1136/gut.42.5.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Keller G., Rotter M., Vogelsang H., Bischoff P., Becker K. F., Mueller J., Brauch H., Siewert J. R., Höfler H. Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history. Am J Pathol. 1995 Sep;147(3):593–600. [PMC free article] [PubMed] [Google Scholar]
  15. Konishi M., Kikuchi-Yanoshita R., Tanaka K., Muraoka M., Onda A., Okumura Y., Kishi N., Iwama T., Mori T., Koike M. Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer. Gastroenterology. 1996 Aug;111(2):307–317. doi: 10.1053/gast.1996.v111.pm8690195. [DOI] [PubMed] [Google Scholar]
  16. LAUREN P. THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. Acta Pathol Microbiol Scand. 1965;64:31–49. doi: 10.1111/apm.1965.64.1.31. [DOI] [PubMed] [Google Scholar]
  17. Liu B., Farrington S. M., Petersen G. M., Hamilton S. R., Parsons R., Papadopoulos N., Fujiwara T., Jen J., Kinzler K. W., Wyllie A. H. Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med. 1995 Apr;1(4):348–352. doi: 10.1038/nm0495-348. [DOI] [PubMed] [Google Scholar]
  18. Mecklin J. P., Nordling S., Saario I. Carcinoma of the stomach and its heredity in young patients. Scand J Gastroenterol. 1988 Apr;23(3):307–311. doi: 10.3109/00365528809093870. [DOI] [PubMed] [Google Scholar]
  19. Myeroff L. L., Parsons R., Kim S. J., Hedrick L., Cho K. R., Orth K., Mathis M., Kinzler K. W., Lutterbaugh J., Park K. A transforming growth factor beta receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res. 1995 Dec 1;55(23):5545–5547. [PubMed] [Google Scholar]
  20. Nakashima H., Inoue H., Mori M., Ueo H., Ikeda M., Akiyoshi T. Microsatellite instability in Japanese gastric cancer. Cancer. 1995 Mar 15;75(6 Suppl):1503–1507. doi: 10.1002/1097-0142(19950315)75:6+<1503::aid-cncr2820751520>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  21. Ottini L., Palli D., Falchetti M., D'Amico C., Amorosi A., Saieva C., Calzolari A., Cimoli F., Tatarelli C., De Marchis L. Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany. Cancer Res. 1997 Oct 15;57(20):4523–4529. [PubMed] [Google Scholar]
  22. Sano T., Tsujino T., Yoshida K., Nakayama H., Haruma K., Ito H., Nakamura Y., Kajiyama G., Tahara E. Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas. Cancer Res. 1991 Jun 1;51(11):2926–2931. [PubMed] [Google Scholar]
  23. Schneider B. G., Pulitzer D. R., Brown R. D., Prihoda T. J., Bostwick D. G., Saldivar V., Rodríguez-Martínez H. A., Gutiérrez-Díaz M. E., O'Connell P. Allelic imbalance in gastric cancer: an affected site on chromosome arm 3p. Genes Chromosomes Cancer. 1995 Aug;13(4):263–271. doi: 10.1002/gcc.2870130406. [DOI] [PubMed] [Google Scholar]
  24. Semba S., Yokozaki H., Yamamoto S., Yasui W., Tahara E. Microsatellite instability in precancerous lesions and adenocarcinomas of the stomach. Cancer. 1996 Apr 15;77(8 Suppl):1620–1627. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1620::AID-CNCR30>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  25. Shitara Y., Yokozaki H., Yasui W., Takenoshita S., Nagamachi Y., Tahara E. Mutation of the transforming growth factor-beta type II receptor gene is a rare event in human sporadic gastric carcinomas. Int J Oncol. 1998 May;12(5):1061–1065. doi: 10.3892/ijo.12.5.1061. [DOI] [PubMed] [Google Scholar]
  26. Strickler J. G., Zheng J., Shu Q., Burgart L. J., Alberts S. R., Shibata D. p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail. Cancer Res. 1994 Sep 1;54(17):4750–4755. [PubMed] [Google Scholar]
  27. Tahara E., Semba S., Tahara H. Molecular biological observations in gastric cancer. Semin Oncol. 1996 Jun;23(3):307–315. [PubMed] [Google Scholar]
  28. Tamura G., Maesawa C., Suzuki Y., Ogasawara S., Terashima M., Saito K., Satodate R. Primary gastric carcinoma cells frequently lose heterozygosity at the APC and MCC genetic loci. Jpn J Cancer Res. 1993 Oct;84(10):1015–1018. doi: 10.1111/j.1349-7006.1993.tb02794.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tamura G., Sakata K., Maesawa C., Suzuki Y., Terashima M., Satoh K., Sekiyama S., Suzuki A., Eda Y., Satodate R. Microsatellite alterations in adenoma and differentiated adenocarcinoma of the stomach. Cancer Res. 1995 May 1;55(9):1933–1936. [PubMed] [Google Scholar]
  30. Thibodeau S. N., Bren G., Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993 May 7;260(5109):816–819. doi: 10.1126/science.8484122. [DOI] [PubMed] [Google Scholar]
  31. Thibodeau S. N., French A. J., Cunningham J. M., Tester D., Burgart L. J., Roche P. C., McDonnell S. K., Schaid D. J., Vockley C. W., Michels V. V. Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res. 1998 Apr 15;58(8):1713–1718. [PubMed] [Google Scholar]
  32. Toh Y., Oki E., Oda S., Tomoda M., Tomisaki S., Ichiyoshi Y., Ohno S., Sugimachi K. An integrated microsatellite length analysis using an automated fluorescent DNA sequencer. Cancer Res. 1996 Jun 15;56(12):2688–2691. [PubMed] [Google Scholar]
  33. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  34. Weber J. L., Kwitek A. E., May P. E., Wallace M. R., Collins F. S., Ledbetter D. H. Dinucleotide repeat polymorphisms at the D17S250 and D17S261 loci. Nucleic Acids Res. 1990 Aug 11;18(15):4640–4640. [PMC free article] [PubMed] [Google Scholar]
  35. Weber J. L., May P. E. Dinucleotide repeat polymorphism at the D18S34 locus. Nucleic Acids Res. 1990 Jun 11;18(11):3431–3431. doi: 10.1093/nar/18.11.3431-a. [DOI] [PMC free article] [PubMed] [Google Scholar]

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