Differential Gene Expression in Familial Pancreatic Cancer Detected by Representational Difference Analysis (RDA)
Abstracts
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Background: It is estimated that as many as 10% of all pancreatic cancers (PCA) result from some type of genetic predisposition. Although genetic abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to explore genetic changes in patients with familial PCA. Methods: Familial PCA was defined as having one or more first degree relatives with biopsy proven adenocarcinoma of the pancreas. Using a PCR based subtractive and kinetic enrichment procedure, RDA, cDNA was reverse transcribed from pooled poly(A)+ mRNA from 6 such patients and compared to pooled cDNA from 5 victims of vehicular trauma. Tumor specific gene fragments were identified and confirmed to be over expressed in familial PCA by competitive rt-PCR using intron spanning gene specific primers and a globally expressed housekeeping gene, GPI. Sporadic PCA (n=12), neuroendocrine tumors of the pancreas (n=5) and chronic pancreatitis tissue (n=3) were screened to determine the specificity of these genes for familial PCA. Results: Sequence analysis revealed homologies to multiple genes of unknown significance (LINE and SINE elements) and 6 genes previously described in neoplasia or carcinogenesis. Most of these genes were not specific to familial PCA. (table) Conclusions: The pattern of frequency in all screened tissue suggests that most of these genes are associated with conditions that produce a significant desmoplastic response. Apolipoprotein A4 was preferentially expressed in familial patients, however, suggesting that the importance of fatty acid synthesis in carcinogenesis should be investigated further. |
