Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma

We have used comparative genomic hybridization (CGH) to survey genomic regions with aberrant copy numbers of DNA sequences in pancreatic adenocarcinoma. In 12 cell lines and 6 primary tumors from 18 patients with pancreatic adenocarcinomas, highly frequent losses (>60%) were observed on chromosome arms 6q, 9p, and 18q and the Y chromosome. Moderately frequent losses (40–60%) were observed on chromosome arms 3p, 4q, 8p, and 21q. Interestingly, these samples showed extremely high frequencies of increases in copy numbers of DNA sequences on the long arm of chromosome 20 (15/18, 83%). We further analyzed five cell lines by fluorescence in situ hybridization (FISH) with probes on chromosome 20 to define the increase in copy number more accurately, and we found that 20q was increased to between 5 and 8 copies per cell. These results suggest the existence of an oncogene or oncogenes on 20q that play a role in the development and/or the progression of pancreatic carcinogenesis. Genes Chromosom. Cancer 19:161–169, 1997. © 1997 Wiley‐Liss Inc.

[1]  A. Horii,et al.  Detailed deletion mapping on chromosome arm 12q in human pancreatic adenocarcinoma: Identification of a 1‐cM region of common allelic loss , 1996, Genes, chromosomes & cancer.

[2]  Scott E. Kern,et al.  DPC4, A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1 , 1996, Science.

[3]  R. Hruban,et al.  Allelotype of pancreatic adenocarcinoma using xenograft enrichment. , 1995, Cancer research.

[4]  S. Hilsenbeck,et al.  Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. , 1995, The American journal of pathology.

[5]  H. Döhner,et al.  Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses. , 1995, Blood.

[6]  S. Bohlander,et al.  Consistent chromosome abnormalities in adenocarcinoma of the pancreas. , 1995, Cancer research.

[7]  W. Kuo,et al.  A physical map of chromosome 20 established using fluorescence in situ hybridization and digital image analysis. , 1995, Genomics.

[8]  S. Devries,et al.  Identification of gains and losses of DNA sequences in primary bladder cancer by comparative genomic hybridization , 1995, Genes, chromosomes & cancer.

[9]  S. Devries,et al.  Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. , 1994, The American journal of pathology.

[10]  R. Hruban,et al.  Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma , 1994, Nature Genetics.

[11]  W. Kuo,et al.  Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes. , 1994, Cancer research.

[12]  R. Hruban,et al.  p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. , 1994, Cancer research.

[13]  N. Pellegata,et al.  K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. , 1994, Cancer research.

[14]  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.

[15]  S. Goodman,et al.  K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. , 1993, The American journal of pathology.

[16]  Y. Nakamura,et al.  High-resolution cytogenetic mapping of 342 new cosmid markers including 43 RFLP markers on human chromosome 17 by fluorescence in situ hybridization. , 1993, Genomics.

[17]  F. Mitelman,et al.  Karyotypic abnormalities in tumours of the pancreas. , 1993, British Journal of Cancer.

[18]  A. Andrén-sandberg,et al.  Nonrandom chromosomal rearrangements in pancreatic carcinomas , 1992, Cancer.

[19]  A. Tanigami,et al.  Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. , 1990, Cancer research.

[20]  D. Shibata,et al.  Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes , 1988, Cell.

[21]  D M Parkin,et al.  Estimates of the worldwide frequency of sixteen major cancers in 1980 , 1988, International journal of cancer.

[22]  M. Kan,et al.  Establishment of six human pancreatic cancer cell lines and their sensitivities to anti-tumor drugs. , 1986, The Tohoku journal of experimental medicine.

[23]  S. Matsuno,et al.  Recent Advances in Diagnosis and Surgical Treatment of Pancreatic Cancer , 1993 .