DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer.

Purpose: Contrary to the extensive data accumulated regarding pancreatic carcinogenesis, the clinical and molecular features characteristic of advanced stage (stage III and IV) disease are unknown. A comprehensive study of pancreatic cancers from patients who have succumbed to their disease has the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention.

Materials And Methods: Rapid autopsies were performed on 76 patients with documented pancreatic cancer.

Frequent genomic copy number gain and overexpression of GATA-6 in pancreatic carcinoma.

Multiple genetic alterations are well recognized as contributing to pancreatic carcinogenesis, although the finding of recurrent copy number changes indicates additional targets remain to be found. The objective of this study was to identify novel targets of genetic alteration that contribute to pancreatic cancer development or progression. We used Representational Oligonucleotide Microarray Analysis (ROMA) to identify copy number changes in pancreatic cancer xenografts, and validated these findings using FISH, quantitative PCR, Western blotting and immunohistochemical labeling.

Evaluation of GATA-4 and GATA-5 methylation profiles in human pancreatic cancers indicate promoter methylation patterns distinct from other human tumor types.

The GATA-4 and GATA-5 transcription factors are increasingly recognized as playing a role in carcinogenesis of human tumors derived of endodermal and mesodermal origin. The pancreas is derived from endodermal tissues suggesting GATA-4 and GATA-5 gene methylation may play a critical role in the biology of human pancreatic cancer as well. We investigated GATA-4 and -5 by methylation-specific PCR (MSP) in normal and neoplastic pancreatic tissues, including isogenic xenografts or cultured cell lines derived from the coexistent primary cancer and/or metastases in patients with pancreatic carcinoma.

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status.

EphA2 is a transmembrane receptor tyrosine kinase that functions in the regulation of cell growth, survival, angiogenesis, and migration and EphA2 targeting has been proposed as a novel therapeutic strategy for neoplasms that overexpress this protein. EphA2 overexpression has been correlated with increased invasive and metastatic ability in pancreatic cancer cell lines. However, the patterns of EphA2 expression in human pancreatic cancers and associated metastases is unknown, as are the genetics of EphA2 in this tumor type.

Identification of chromosomal imbalances in pancreatic carcinoma using comparative genomic hybridization.

Objective: To identify genetic abnormalities in primary pancreatic carcinoma in humans.

Methods: Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in 27 cases of pancreatic carcinomas. Multiple deletions and gains were observed in all tumor specimens.