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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Oct;84(10):1015–1018. doi: 10.1111/j.1349-7006.1993.tb02794.x

Primary Gastric Carcinoma Cells Frequently Lose Heterozygosity at the APC and MCC Genetic Loci

Gen Tamura 1,✉, Chihaya Maesawa 1, Yasushi Suzuki 1, Satoshi Ogasawara 1, Masanori Terashima 2, Kazuyoshi Saito 2, Ryoichi Satodate 1
PMCID: PMC5919060  PMID: 8226275

Abstract

Loss of heterozygosity (LOH) at APC and MCC gene loci (both mapped to 5q21) was investigated in 24 surgical specimens of primary gastric carcinomas using the polymerase chain reaction after tumor cell enrichment by cell sorting based on differences in DNA content. LOH at APC and/or MCC was detected in 87% (13/15) of the cases; at the APC in 86% (12/14) and at the MCC locus in 100% (7/7). LOH at the APC locus was always accompanied by LOH at the MCC locus. LOH at the APC and/or MCC was found in both differentiated and undifferentiated types in both early and advanced stages of gastric carcinoma. Thus, LOH at APC and/or MCC is considered to be one of the most prevalent genetic alterations in human gastric carcinoma and occurs at an early stage of the carcinogenesis.

Keywords: Loss of heterozygosity, APC gene, MCC gene, Gastric carcinoma, Polymerase chain reaction

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REFERENCES

  • 1).Joslyn , G. , Carlson , M. , Thliveris , A. , Albertsen , H. , Gelbert , L. , Samowitz , W. , Groden , J. , Stevens , J. , Spirio , L. , Robertson , M. , Sargeant , L. , Krapcho , K. , Wolff , E. , Burt , R. , Hughes , J. P. , Warrington , J. , McPherson , J. , Wasmuth , J. , LePaslier , D. , Abderrahim , H. , Cohen , D. , Leppert , M. and White , R.Identification of deletion mutations and three new genes at the familial polyposis locus . Cell , 66 , 601 – 613 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 2).Kinzler , K. W. , Nilbert , M. C. , Su , L‐K. , Vogelstein , B. , Bryan , T. M. , Levy , D. B. , Smith , K. J. , Preisinger , A. C. , Hedge , P. , McKechnie , D. , Finniear , R. , Markham , A. , Groffen , J. , Boguski , M. S. , Altschul , S. F. , Horii , A. , Ando , H. , Miyoshi , Y. , Miki , Y. , Nishisho , I. and Nakamura , Y.Identification of FAP locus genes from chromosome 5q21 . Science , 253 , 661 – 665 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 3).Kinzler , K. W. , Nilbert , M. C. , Vogelstein , B. , Bryan , T. M. , Levy , D. B. , Smith , K. J. , Preisinger , A. C. , Hamilton , S. R. , Hedge , P. , Markham , A. , Carlson , M. , Joslyn , G. , Groden , J. , White , R. , Miki , Y. , Miyoshi , Y. , Nishisho , I. and Nakamura , Y.Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers . Science , 251 , 1366 – 1370 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 4).Nishisho , I. , Nakamura , Y. , Miyoshi , Y. , Miki , Y. , Ando , H. , Horii , A. , Koyama , K. , Utsunomiya , J. , Baba , S. , Hedge , P. , Markham , A. , Krusti , A. J. , Petersen , G. , Hamilton , S. R. , Nilbert , M. C. , Levy , D. B. , Bryan , T. M. , Preisinger , A. C. , Smith , K. J. , Su , L‐K. , Kinzler , K. W. and Vogelstein , B.Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients . Science , 253 , 665 – 669 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 5).Miyoshi , Y. , Nagase , H. , Ando , H. , Horii , A. , Ichii , S. , Nakatsuru , S. , Aoki , T. , Miki , Y. , Mori , T. and Nakamura , Y.Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene . Hum. Mol. Genet. , 1 , 229 – 233 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 6).Miyoshi , Y. , Ando , H. , Nagase , H. , Nishisho , I. , Horii , A. , Miki , Y. , Mori , T. , Utsunomiya , J. , Baba , S. , Peterson , G. , Hamilton , S. R. , Kinzler , K. W. , Vogelstein , B. and Nakamura , Y.Germ‐line mutations of the APC gene in 53 familial adenomatous polyposis patients . Proc. Natl. Acad. Sci. USA , 89 , 4452 – 4456 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7).Greenwald , B. D. , Harpaz , N. , Yin , J. , Huang , Y. , Tong , Y. , Brown , V. L. , McDaniel , T. , Newkirk , C. , Resau , J. H. and Meltzer , S. J.Loss of heterozygosity affecting the p53, Rb and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis . Cancer Res. , 52 , 741 – 745 ( 1992. ). [PubMed] [Google Scholar]
  • 8).Boynton , R. F. , Blount , P. L. , Yin , J. , Brown , V. L. , Huang , Y. , Tong , Y. , McDaniel , T. , Newkirk , C. , Resau , J. H. , Raskind , W. H. , Haggitt , R. C. , Reid , B. J. and Meltzer , S. J.Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers . Proc. Natl. Acad. Sci. USA , 89 , 3385 – 3388 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9).D'Amico , D. , Carbone , D. P. , Johnson , B. E. , Meltzer , S. J. and Minna , J. D.Polymorphic sites within the MCC and APC loci reveal very frequent loss of heterozygosity in human small cell lung cancer . Cancer Res. , 52 , 1996 – 1999 ( 1992. ). [PubMed] [Google Scholar]
  • 10).Horii , A. , Nakatsuru , S. , Miyoshi , Y. , Ichii , S. , Nagase , H. , Kato , Y. , Yanagisawa , A. and Nakamura , Y.The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer . Cancer Res. , 52 , 3231 – 3233 ( 1992. ). [PubMed] [Google Scholar]
  • 11).Horii , A. , Nakatsuru , S. , Miyoshi , Y. , Ichii , S. , Nagase , H. , Ando , H. , Yanagisawa , A. , Tsuchiya , E. , Kato , Y. and Nakamura , Y.Frequent somatic mutations of the APC gene in human pancreatic cancer . Cancer Res. , 52 , 6696 – 6698 ( 1992. ). [PubMed] [Google Scholar]
  • 12).Nigro , J. M. , Baker , S. J. , Preisinger , A. C. , Jessup , J. M. , Hosteller , R. , Cleary , K. , Binger , S. H. , Davidson , N. , Baylin , S. , Devilee , P. , Glover , T. , Collins , F. S. , Weston , A. , Modali , R. , Harris , C. C. and Vogelstein , B.Mutations in the p53 gene occur in diverse human tumor types . Nature , 342 , 705 – 708 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 13).Tamura , G. , Kihana , T. , Nomura , K. , Terada , M. , Sugimura , T. and Hirohashi , S.Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single‐strand conformation polymorphism analysis . Cancer Res. , 51 , 3056 – 3058 ( 1991. ). [PubMed] [Google Scholar]
  • 14).Maesawa , C. , Tamura , G. , Suzuki , Y. , Ishida , K. , Saito , K. and Satodate , R.Sensitive detection of p53 gene mutations in esophageal endoscopic biopsy specimens by cell sorting combined with polymerase chain reaction single‐strand conformation polymorphism analysis . Jpn. J. Cancer Res. , 83 , 1253 – 1256 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15).Burmer , G. C. and Loeb , L. A.Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma . Proc. Natl. Acad. Sci. USA , 86 , 2403 – 2407 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16).Hirohashi , S. and Sugimura , T.Genetic alterations in human gastric cancer . Cancer Cells , 3 , 49 – 52 ( 1991. ). [PubMed] [Google Scholar]
  • 17).Sano , T. , Tsujino , T. , Yoshida , K. , Nakayama , H. , Haruma , K. , Ito , H. , Nakamura , Y. , Kajiyama , G. and Tahara , E.Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas . Cancer Res. , 51 , 2926 – 2931 ( 1991. ). [PubMed] [Google Scholar]
  • 18).Tahara , E.Molecular mechanism of stomach carcinogenesis . J. Cancer Res., Clin. Oncol. , 119 , 1 – 8 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 19).Ding , S.‐F. , Habib , N. A. , Dooley , J. , Wood , C. , Bowles , L. and Delhanty , J. D. A.Loss of constitutional heterozygosity on chromosome 5q in hepatocellular carcinoma without cirrhosis . Br. J. Cancer , 64 , 1083 – 1087 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

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