Changes in DNA copy number in primary gastric carcinomas by comparative genomic hybridization.

We examined 33 primary gastric carcinomas using comparative genomic hybridization to detect changes in the DNA copy number and the chromosomal location of these changes. Ninety-four percent (31 of 33) showed 1 or more DNA copy number changes, such as increases at 2p23-p25 (observed in 21% of the total cases), 3q26.3-q27 (24%), 7p15 (24%), 9p22-pter (18%), and 13q22-q34 (21%) and decreases at 1p34.2-p36.2 (18%) and Y (52%). Histological examination indicated that increases at 3q26.1-q26.3 and 7p15 and decreases at 1p36.1-p36. 2 and Y were commonly observed in both differentiated and undifferentiated types. Increases at 3q27, 6q23-q25, and 7cen-p14 and decreases at 1p34.2-p35 and 17p12 were predominantly observed in the differentiated type, and increases at 2p23-pter, 9p22-pter, and 13q31-qter and a decrease at 6p21.3 were predominantly observed in the undifferentiated type. In addition, clinical staging of tumors showed that increases at 2p23-p25, 7p14-p21, 7q31-q32, and 9p22-pter and a decrease at Y were observed in early-stage tumors, whereas increases at 9q32-q33 and 15q26 were observed only in late-stage tumors. Many of the abnormalities detected in this study were not previously reported in gastric carcinomas. Our comparative genomic hybridization results indicate the presence of genetic alterations that may play some important role in the development and progression of gastric carcinomas.

[1]  J. Gray,et al.  Identification of novel regions of altered DNA copy number in small cell lung tumors , 1995, Genes, chromosomes & cancer.

[2]  M. Karpeh,et al.  Immunohistochemical evaluation of bcl‐2 protein expression in gastric adenocarcinomas , 1995, Cancer.

[3]  T. Okuda,et al.  Clinical significance of epidermal growth factor (EGF), EGF receptor, and c‐erbb‐2 in human gastric cancer , 1995, Cancer.

[4]  S. Knuutila,et al.  Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. , 1995, Cancer research.

[5]  D. Ward,et al.  Comparative genomic hybridization detects novel deletions and amplifications in head and neck squamous cell carcinomas. , 1995, Cancer research.

[6]  T. Visakorpi,et al.  Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization. , 1995, Cancer research.

[7]  M R Speicher,et al.  Chromosomal gains and losses in uveal melanomas detected by comparative genomic hybridization. , 1994, Cancer research.

[8]  M. Seto,et al.  Loss of Heterozygosity at the bcl‐2 Gene Locus and Expression of bcl‐2 in Human Gastric and Colorectal Carcinomas , 1994, Japanese journal of cancer research : Gann.

[9]  J Piper,et al.  Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Furui,et al.  erbB-2 expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. , 1994, Surgery.

[11]  M. Satoh,et al.  Mutations of the APC gene occur during early stages of gastric adenoma development. , 1994, Cancer research.

[12]  S. Fushida,et al.  Amplification of the c-erbB-2 gene in gastric carcinoma: correlation with survival. , 1993, Oncology.

[13]  Y. Furukawa,et al.  Somatic mutations of the APC gene in precancerous lesion of the stomach. , 1993, Human molecular genetics.

[14]  D. Amadori,et al.  Base transitions are the most frequent genetic changes at P53 in gastric cancer. , 1993, Cancer research.

[15]  T. Yoshikawa,et al.  Predictive value of c-erbB-2 and DNA ploidy patterns in gastric carcinoma recurrence. , 1993, International surgery.

[16]  D. Amadori,et al.  DNA amplification in human gastric carcinomas. , 1993, Cancer genetics and cytogenetics.

[17]  D Rutovitz,et al.  Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors. , 1993, Seminars in cancer biology.

[18]  P. Comoglio,et al.  Karyotypic analysis of gastric carcinoma cell lines carrying an amplified c-met oncogene. , 1992, Cancer genetics and cytogenetics.

[19]  H. Ito,et al.  Frequent amplification of the c-met gene in scirrhous type stomach cancer. , 1992, Biochemical and biophysical research communications.

[20]  Y. Nakamura,et al.  Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma. , 1992, Human molecular genetics.

[21]  R. Seruca,et al.  Loss of Y chromosome in gastric carcinoma. Fact or artifact? , 1992, Cancer genetics and cytogenetics.

[22]  S Ichii,et al.  The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer. , 1992, Cancer research.

[23]  S. Hirohashi,et al.  Frequent loss of heterozygosity at the DCC locus in gastric cancer. , 1992, Cancer research.

[24]  T Matozaki,et al.  Missense mutations and a deletion of the p53 gene in human gastric cancer. , 1992, Biochemical and biophysical research communications.

[25]  S. Hirohashi,et al.  p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases. , 1991, Cancer research.

[26]  J. Minna,et al.  Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines. , 1991, Journal of the National Cancer Institute.

[27]  N. Lemoine,et al.  Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. , 1991, British Journal of Cancer.

[28]  J. Yokota,et al.  Isolation of an Amplified DNA Sequence in Stomach Cancer , 1990, Japanese journal of cancer research : Gann.

[29]  J. Yokota,et al.  Infrequent loss of chromosomal heterozygosity in human stomach cancer. , 1988, Cancer research.

[30]  B J Williams,et al.  Comparative genomic hybridization. , 1996, Methods in molecular medicine.

[31]  S. Manoir,et al.  Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses. , 1994, The American journal of pathology.

[32]  H. Müller-Hermelink,et al.  Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma , 1993, Virchows Archiv. B, Cell pathology including molecular pathology.

[33]  T. Kameda,et al.  Tyrosine kinase activity of epidermal growth factor receptor in human gastric carcinomas. , 1992, Pathology, research and practice.