Detailed deletion mapping on chromosome arm 12q in human pancreatic adenocarcinoma: Identification of a 1‐cM region of common allelic loss

As a first step toward understanding molecular mechanisms in human pancreatic carcinogenesis, we searched for the location of tumor suppressor genes by examining loss of heterozygosity (LOH) in 44 pancreatic cancer specimens. We used 46 microsatellite markers that spanned all of the autosomes. Frequent LOH was observed in six chromosomal regions: in chromosome arms 1p (32%), 6q (37%), 9p (50%), 12q (30%), 17p (59%), and 18q (35%). Because chromosome arm 12q is a reported target for allelic loss in some other cancers, we focused on this region with 66 primary specimens and identified the minimal common region of allelic loss within a 1‐cM interval in 12q22‐q23.1. Microsatellite instability (MI) was also examined in this study, and the incidence of MI(+) cases, in which MI of two or more microsatellite loci was detected, was 61% (27 of 44 informative cases). In pancreatic tumors with MI(+), mutations of the transforming growth factor β receptor II (RII) gene were not detected. Genes Chromosom Cancer 17:88–93 (1996). © 1996 Wiley‐Liss, Inc.

[1]  K. Kinzler,et al.  Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. , 1995, Cancer research.

[2]  Kathleen R. Cho,et al.  A transforming growth factor beta receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. , 1995, Cancer research.

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

[4]  M. Kimmey,et al.  Microsatellite instability and K-ras mutations associated with pancreatic adenocarcinoma and pancreatitis. , 1995, Cancer research.

[5]  P. O'Connell,et al.  Allelic imbalance in gastric cancer: An affected site on chromosome arm 3p , 1995, Genes, chromosomes & cancer.

[6]  K. Kinzler,et al.  Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. , 1995, Science.

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

[8]  Y. Nakamura,et al.  Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. , 1994, Cancer Research.

[9]  Cécile Fizames,et al.  The 1993–94 Généthon human genetic linkage map , 1994, Nature Genetics.

[10]  C Caldas,et al.  Allelotype of pancreatic adenocarcinoma. , 1994, Cancer research.

[11]  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.

[12]  R. Hruban,et al.  Chromosome abnormalities in pancreatic adenocarcinoma , 1994, Genes, chromosomes & cancer.

[13]  J. Cairns,et al.  Allelotype of human bladder cancer. , 1994, Cancer research.

[14]  Y. Nakamura,et al.  Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. , 1993, Cancer research.

[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]  A. Andrén-sandberg,et al.  Karyotypic abnormalities in tumours of the pancreas. , 1993, British Journal of Cancer.

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

[18]  S Ichii,et al.  Frequent somatic mutations of the APC gene in human pancreatic cancer. , 1992, Cancer research.

[19]  V. Reuter,et al.  Allelic deletions in the long arm of chromosome 12 identify sites of candidate tumor suppressor genes in male germ cell tumors. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Y. Nakamura,et al.  Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma. , 1992, Cancer research.

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

[22]  R. Hutter.  From the editor‐in‐chief: Changing of the guard , 1992 .

[23]  Y. Nakamura,et al.  Accumulation of genetic alterations and progression of primary breast cancer. , 1991, Cancer research.

[24]  A. Yanagisawa,et al.  c‐Ki‐rasPoint Mutations in Ductectatic‐type Mucinous Cystic Neoplasms of the Pancreas , 1991, Japanese journal of cancer research : Gann.

[25]  Y. Nakamura,et al.  Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas. , 1991, Cancer research.

[26]  R. White,et al.  Allelotype of human malignant astrocytoma. , 1990, Cancer research.

[27]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[28]  M. Fey,et al.  Clonal allele loss in gastrointestinal cancers. , 1989, British Journal of Cancer.

[29]  B. Vogelstein,et al.  Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. , 1985, Biochemical and biophysical research communications.