Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 Jul;92(7):740–747. doi: 10.1111/j.1349-7006.2001.tb01156.x

DNA Sequence Copy Number Aberrations Associated with Histological Subtypes and DNA Ploidy in Gastric Carcinoma

Gu Kong 1,, Atsunori Oga 2, Chan Kum Park 1, Shigeto Kawauchi 2, Tomoko Furuya 2, Kohsuke Sasaki 2,
PMCID: PMC5926784  PMID: 11473724

Abstract

We have analyzed DNA sequence copy number aberrations (DSCNAs) and DNA ploidy by using comparative genomic hybridization and laser scanning cytometer in gastric carcinomas (GCs) to elucidate the genomic aberrations in relation to clinicopathological parameters. Thirty‐two out of 33 cases showed one or more DSCNAs with a mean number of 11.7 per tumor. High‐level gains were detected at 2p, 3q, 6p, 7p, 7q, 8q, 12p, 13q, 19q, and 20q. Frequency of gross genomic abnormalities and chromosome regions that have genomic aberrations were similar in both intestinal‐and diffuse‐type GCs, except aberrations at 8p, 9p, 12q, and 20q. The overall number of DSCNAs was significantly greater in DNA aneuploid tumors than that in DNA diploid tumors. We detected genomic aberrations characterized by histological subtype, tumor location, and DNA ploidy status: gain of 20q and losses of 8p and 9p in intestinal‐type GCs, gains of 8p and 12q in diffuse‐type GCs, gain of 20q in the lower third GCs, and loss of 5q, 9p, lOq, 16q, and 18q in DNA aneuploid GCs. Furthermore, 5q loss is associated with DNA aneuploidy (P=0.0001) or the total number of losses (P=0.001), gain+losses (P=0.004), and high‐level gains (P=0.001) in GCs. Among these loci, chromosome 8p was unique. Gain of 8p was more common in diffuse‐type GC, whereas loss of 8p was more frequently detected in intestinal‐type GC. In conclusion, we describe chromosomal regions of 5q, 8p, and 20q, which are of interest for further investigation of GCs.

Keywords: Comparative genomic hybridization, Data base, Gastric cancer, Genomic aberration, Laser scanning cytometry

Full Text

The Full Text of this article is available as a PDF (142.4 KB).

Reference

  • 1.Correa , P. and Shiao , Y. H.Phenotypic and genotypic events in gastric carcinogenesis . Cancer Res. , 54 , 1941 – 1943 ( 1994. ). [PubMed] [Google Scholar]
  • 2.Tahara , E. , Semba , S. and Tahara , H.Molecular biological observations in gastric cancer . Semin. Oncol. , 23 , 307 – 315 ( 1994. ). [PubMed] [Google Scholar]
  • 3.Lauren , P . The two histological main types of gastric adenocarcinoma. Diffuse and so called intestinal‐type carcinoma . Acta Pathol. Microbiol. Scand. , 64 , 31 – 49 ( 1965. ). [DOI] [PubMed] [Google Scholar]
  • 4.Becker , K.F. , Atkinson , M.J. , Reich , U. , Becker , I. , Nekarda , H. , Siewert , J. R. and Hofler , H.E‐Cadherin gene mutations provide clues to diffuse type gastric carcinomas . Cancer Res. , 54 , 3845 – 3852 ( 1994. ). [PubMed] [Google Scholar]
  • 5.Kuniyasu , H. , Yasui , W. , Kitadai , Y. , Yokozaki , H. , Ito , H. and Tahara , E.Frequent amplification of the c‐met gene in scirrhous type stomach cancer . Biochem. Biophys.Res. Commun. , 189 , 227 – 232 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 6.Tamura , G. , Sakata , K. , Nishizuka , S. , Maesawa , C. , Suzuki , Y. , Iwaya , T. , Terashima , M. , Saito , K. and Satodate , R.Inactivation of the E‐cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines . Jpn. J. Cancer Res. , 87 , 1153 – 1159 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Kallioniemi , A. , Kallioniemi , O.‐P. , Sudar , D. , Rutovitz , D. , Gray , J. W. , Waldman , F. and Pinkel , D.Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors . Science , 258 , 818 – 821 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 8.Kusano , N. , Shiraishi , K. , Kubo , K. , Oga , A. , Okita , K. and Sasaki , K.Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: their relationship to clinicopathological features . Hepatology , 29 , 1858 – 1862 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 9.Tada , K. , Oka , M. , Tangoku , A. , Hayashi , H. , Oga , A. and Sasaki , K.Gains of 8q23‐qter and 20q and losses of 11q22‐qterassociated with lymph node metastasis in esophageal squamous cell carcinoma . Cancer , 88 , 268 – 273 ( 2000. ). [DOI] [PubMed] [Google Scholar]
  • 10.Hashimoto , Y. , Oga , A. , Okami , K. , Imate , Y. , Yamashita , Y. and Sasaki , K.Relationship between cytogenetic aberrationsbyCGH coupledwithtissuemicrodissectionand DNA ploidy by laser scanning cytometry in head and neck squamous cell carcinoma . Cytometry 40 , 161 – 166 ( 2000. ). [PubMed] [Google Scholar]
  • 11.Koizumi , Y. , Tanaka , S. , Mou , R. , Koganei , H. , Kokawa , A. , Kitamura , R. , Yamaguchi , H. , Ookubo , K. , Saito , T. , Tominaga , S. , Matsumura , K. , Shimada , H. , Tsuchida , N. and Sekihara , H.Change in DNA copy number in primary gastric carcinomas by comparative genomic hybridization . Clin. Cancer Res. , 3 , 1067 – 1076 ( 1997. ). [PubMed] [Google Scholar]
  • 12.Kokkola , A. , Monni , O. , Puolakkainen , P. , Larramendy , M. L. , Victorzon , M. , Nordling , S. , Haapiainen , R. , Kivilaakso , E. and Knuutila , S.17ql2‐21 amplicon, a novel recurrent genetic change in intestinal type of gastric carcinoma: a comparative genomic hybridization study . Genes Chromosom. Cancer , 20 , 38 – 43 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 13.Nessling , M. , Solinas‐Toldo , S. , Wilgenbus , K.K. , Borchard , F. and Lichter , P.Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2 . Genes Chromosom. Cancer , 23 , 307 – 316 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 14.El‐Rifai , W. , Harper , J. C. , Cummings , O. W. , Hyytinen , E. R. , Frierson , H. F. , Jr. , Knuutila , S. and Powell , S. M.Consistent genetic alterations in xenografts of proximal stomach and gastro‐esophageal junction adenocarcinomas . Cancer Res. , 58 , 34 – 37 ( 1998. ). [PubMed] [Google Scholar]
  • 15.van Dekken , H. , Geelen , E. , Dinjens , W. N. M. , Wijnhoven , B. P. L. , Tilanus , H. W. , Tanke , H. J. and Rosenberg , C.Comparative genomic hybridization of cancer of the gastroesophageal junction:deletion of 14q31‐32.1discriminatesbetweenesophageal(Barrett's)andgastriccardia adenocarcinomas . Cancer Res. , 59 , 748 – 752 ( 1999. ). [PubMed] [Google Scholar]
  • 16.Wu , M. S. , Chang , M. C. , Huang , S. P. , Tseng , C. C. , Sheu , J. C. , Lin , Y. W. , Shun , C. T. , Lin , M. T. and Lin , J. T.Correlation of histologic subtypes and replication error phenotype with comparative genomic hybridization in gastric cancer . Genes Chromosom. Cancer , 30 , 80 – 86 ( 2001. ). [DOI] [PubMed] [Google Scholar]
  • 17.Oga , A. , Kong , G. , Ishii , Y. , Izumi , H. , Park , C. Y. and Sasaki , K.Preferential loss of 5ql4‐21 in intestinal‐type gastric cancer with DNA aneuploidy . Cytometry , 46 , 57 – 62 ( 2001. ). [PubMed] [Google Scholar]
  • 18.Nishizaki , T. , DeVries , S. , Chew , K. , Goodson , W. H. , Ljung , B. M. , Thor , A. and Waldman , F. M.Genetic alterations inprimarybreast cancers and theirmetastases. Direct comparisonusing modified comparative genomic hybridization . Genes ChromosomCancer , 19 , 267 – 272 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 19.Nishizaki , T. , Chew , K. , Chu , L. , Isola , J. , Kallioniemi , A. , Weidner , N. and Waldman , F. M.Genetic alterations in lobular breast cancer by comparative genomic hybridization . Int. J. Cancer , 74 , 513 – 517 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 20.Kamentsky , L. A. and Kamentsky , L. D.Microscope‐based multiparameter laser scanning cytometer yielding data comparable to flow cytometry data . Cytometry , 12 , 381 – 387 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21.Sasaki , K. , Kurose , A. , Miura , Y. , Sato , T. and Ikeda , E.DNA ploidy analysis by laser scanning cytometry (LSC) in colorectal cancers and comparison with flow cytometry . Cytometry , 23106 – 109 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 22.Saal , K. , Vollmers , H. P. , Muller , J. , Kohler , J. , Hohn , H. and Muller‐Hermelink , H. K.Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma . Virchows Arch. B , 64 , 145 – 150 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 23.Anzick , S. , Kononen , J. , Walker , R. , Azorsa , D. , Tanner , M. , Guan , X. , Sauter , G. , Kallioniemi , O. , Trent , J. and Meltzer , P. S.AIB1, a steroid receptor coactivator amplification in breast and ovarian cancer . Science , 227 , 965 – 968 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 24.Brinkmann , U. , Gallo , M. , Polymeropoulo , M.H. and Pastan , I.The human CAS (cellular apoptosis susceptibility) gene mapping on chromosome 20ql3 is amplified in BT474 breast cancer cells and part of aberrant chromosomes in breast and colon cancer cell lines . Genome Res. , 6 , 187 – 194 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 25.Fukushige , S. , Waldman , F.M. , Kimura , M. , Abe , T. , Furukawa , T. , Sunamura , M. , Kobari , M. and Horii , A.Frequent gain of copy number on the long arm of chromosome20inhuman pancreaticadenocarcinoma . Genes Chromosom. Cancer , 19 , 161 – 169 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 26.Noben‐Trauth , K. , Copeland , N. G. , Gilbert , D. J. , Jenkins , N. A. , Sonoda , G. , Testa , J. R. and Klempnauer , K.‐H.Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q13.1 . Genomics , 35 , 610 – 612 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 27.Tanner , M. M. , Tirkkonen , M. , Kallioniemi , A. , Isola , J. , Kuukasjarvi , T. , Collins , C. , Kowbel , D. , Guan , X.Y. , Trent , J. , Gray , J. W. , Meltzer , P. and Kallioniemi , O.‐P . Independent amplification and frequent co‐amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer . Cancer Res. , 56 , 3441 – 3445 ( 1996. ). [PubMed] [Google Scholar]
  • 28.Sakakura , C. , Mori , T. , Sakabe , T. , Ariyama , Y. , Shinomiya , T. , Date , K. , Hagiwara , A. , Yamaguchi , T. , Takahashi , T. , Nakamura , Y. , Abe , T. and Inazawa , J.Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization . Genes Chromosom.Cancer , 24 , 299 – 305 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 29.Knuutila , S. , Bjorkqvist , A. M. , Autio , K. , Tarkkanen , M. , Wolf , M. , Monni , O. , Szymanska , J. , Larramendy , M. L. , Tapper , J. , Pere , H. , El‐Rifai , W. , Hemmer , S. , Wasenius , V. M. , Vidgren , V. and Zhu , Y.DNA copy number amplifications in human neoplasms: review ofcomparative genomic hybridization studies . Am. J. Pathol. , 152 , 1107 – 1123 ( 1998. ). Table 2 and reference list were updated in June 1999 . http://www.helsinki.fi/~lgl_www/CGH_Cover_ page.html. [PMC free article] [PubMed] [Google Scholar]
  • 30.Sakabe , T. , Shinomiya , T. , Mori , T. , Ariyama , Y. , Fukuda , Y. , Fujiwara , T. , Nakamura , Y. and Inazawa , J.Identification of a novel gene, MASL1, within an amplicon at 8p23.1 detected in malignant fibrous histiocytomas by comparative genomic hybridization . Cancer Res. , 59 , 511 – 515 ( 1999. ). [PubMed] [Google Scholar]
  • 31.Cher , M. , MacGrogan , D. , Bookstein , R. , Brown , J. , Jenkins , R. and Jensen , R.Comparative genomic hybridization, allelic imbalance, and fluorescence in situ hybridization on chromosome 8 in prostate cancer . Genes Chromosom. Cancer , 11 , 153 – 162 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 32.Fejzo , M. S. , Godfrey , T. , Chen , C. , Waldman , F. and Gray , J. W.Molecular cytogenetic analysis of consistent abnormalities at 8ql2‐q22 in breast cancer . Genes Chromosom. Cancer , 22 , 105 – 113 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 33.Levin , N. , Brzoska , P. , Gupta , N. , Minna , J. , Gray , J. and Christman , M.Identification of frequent novel genetic alterations in small cell lung carcinoma . Cancer Res. , 54 , 5086 – 5091 ( 1994. ). [PubMed] [Google Scholar]
  • 34.Bieche , I. and Lidereau , R.Genetic alterations in breast cancer . Genes Chromosom. Cancer , 14 , 227 – 251 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 35.Maeda , K. , Kang , S. M. , Onoda , N. , Ogawa , M. , Kato , Y. , Sawada , T. and Chung , K. H.Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric cancer . Cancer , 86 , 566 – 571 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 36.Hirono , Y. , Tsugawa , K. , Fushida , S. , Ninomiya , L , Yonemura , Y. , Miyazaki , L , Endou , Y. , Tanaka , M. and Sasaki , T.Amplification of epidermal growth factor receptor gene and its relationship to survival in human gastric cancer . Oncology , 52 , 182 – 188 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 37.Tsugawa , K. , Yonemura , Y. , Hirono , Y. , Fushida , S. , Kaji , M. , Miwa , K. , Miyazaki , I. and Yamamoto , H.Amplification of the c‐met, c‐erbB‐2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features . Oncology , 55 , 475 – 481 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 38.Beround , C. and Soussi , T.APC gene: database of germ‐line and somatic mutations in human tumors and cell lines . Nucleic Acids Res. 24 , 121 – 124 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Tamura , G. , Ogasawara , S. , Nishizuka , S. , Sakata , K. , Maesawa , C. , Suzuki , Y. , Terashima , M. , Saito , K. and Satodate , R.Two distinct regions of deletion on the long arm of chromosome 5 in differentiated adenocarcinomas of the stomach . Cancer Res. , 56 , 612 – 615 ( 1996. ). [PubMed] [Google Scholar]
  • 40.Ming , S. C.Cellular and molecular pathology of gastric carcinoma and precursor lesions: a critical review . Gastric Cancer , 1 , 31 – 50 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 41.Myung , N. , Kim , M. R. , Chung , I. P. , Kim , H. and Jang , J. J.Loss of pi 6 and p27 is associated with progression of human gastric cancer . Cancer Lett , 153 , 129 – 136 ( 2000. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES