Differential gene expression in patients genetically predisposed to pancreatic cancer.
BACKGROUND
Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA.


METHODS
We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes.


RESULTS
Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA.


CONCLUSIONS
The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.
Zervos
Emmanuel E
EE
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, Ohio, USA. zervosee@moffitt.usf.edu
Tanner
Stephan M
SM
Osborne
Dana A
DA
Bloomston
Mark
M
Rosemurgy
Alexander S
AS
Ellison
E Christopher
EC
Melvin
W Scott
WS
de la Chapelle
Albert
A
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019295:Computational Biology; D005260:Female; D005431:Florida; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009820:Ohio; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA