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Pattern of secondary genomic changes in pancreatic tumors of Tgf α/ Trp53 +/− transgenic mice
Author(s) -
Schreiner Bettina,
Baur Dorothee M.,
Fingerle Alexander A.,
Zechner Ulrich,
Greten Florian R.,
Adler Guido,
Sipos Bence,
Klöppel Günter,
Hameister Horst,
Schmid Roland M.
Publication year - 2003
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10285
Subject(s) - loss of heterozygosity , biology , cdkn2a , comparative genomic hybridization , locus (genetics) , genetically modified mouse , pancreatic cancer , chromosome , carcinogenesis , pancreas , chromosome 7 (human) , cancer research , microbiology and biotechnology , methylation , genetics , gene , transgene , allele , cancer , biochemistry
Trp53 +/− mice overexpressing Tgfα in a pancreas‐specific manner represent a well‐established animal model for pancreatic cancer. In this study we analyzed 38 pancreatic adenocarcinomas of these mice for secondary genomic changes by comparative genomic hybridization (CGH), loss of heterozygosity (LOH) analysis, real‐time PCR, and methylation‐specific analysis. CGH screening of the tumors revealed a recurrent pattern of genomic changes. In more than 50% of the tumors, chromosome 11 was affected. The gain of the proximal part spans about 16 cM, including the genes for Egfr , Rel , and Stk10 . The distal part of chromosome 11, which contains the Trp53 locus, was deleted. LOH analysis proved that almost all tumors segregate the wild‐type Trp53 allele. The Cdkn2a locus on chromosome 4 was inactivated by hypermethylation in 55% of all tumors. In addition, two other changes were detected in a mutually exclusive manner: overrepresentation of part of chromosome 15, or more rarely, loss of the distal part of chromosome 14. Together these data suggest the induction of a uniform pattern of secondary genomic changes in this transgenic tumor model for pancreatic cancer. © 2003 Wiley‐Liss, Inc.