Identification of genetic changes associated with the development of intraepithelial ductal neoplasia and those correlating with progression to invasive cancer are expected to provide important clues on the genetic mechanisms causing malignant transformation and progression processes. Such investigations should help develop novel markers for early detection of intraepithelial lesions and those predisposed to progress to invasive cancer. We are proposing to pursue genomics and molecular genetics based approaches to characterize putative target loci on selected specific individual chromosomes, frequently implicated in pancreatic cancer, which harbor genes deleted (""""""""loss of function tumor suppressor genes"""""""") and over expressed in pancreatic cancer (""""""""gain of function oncogenes""""""""). Additionally, we are also proposing to do genome wide microsatellite instability, methylation assays and expression profiling studies between paired normal and tumor samples to identify genetic anomalies associated with initiation and progression of pancreatic cancer. The overall goal of this project is to identify early detection genetic biomarkers for pancreatic cancer with an integrated approach of molecular genetic, genomic array and expression array analyses of tumor tissues, serum and pancreatic juice from pancreatic cancer patients. The chromosomal loci to be studied will include the target tumor suppressor gene(s) harboring chromosomes lp and 3p and minimally amplified regions harboring putative oncogenes on chromosomes 20q and 12p. We hypothesize that pathways involving tumor suppressor genes with loss of function mutations/deletions and dominantly activated/amplified/ over-expressed oncogenes are critical determinants in the development of early phases of pancreatic neoplasia. From these loci, we will be developing locus specific DNA based fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) assays and also protein specific immunochemical detection assays for early detection of intraepithelial pancreatic neoplasia.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZCA1-SRRB-E (O1))
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Wagner, Paul D
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University of Texas MD Anderson Cancer Center
Other Domestic Higher Education
United States
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Balasenthil, Seetharaman; Huang, Ying; Liu, Suyu et al. (2017) A Plasma Biomarker Panel to Identify Surgically Resectable Early-Stage Pancreatic Cancer. J Natl Cancer Inst 109:
Wang, Jin; Chen, Jinyun; Sen, Subrata (2016) MicroRNA as Biomarkers and Diagnostics. J Cell Physiol 231:25-30
Chen, Jinyun; Wu, Xifeng; Huang, Yujing et al. (2016) Identification of genetic variants predictive of early onset pancreatic cancer through a population science analysis of functional genomic datasets. Oncotarget 7:56480-56490
Haab, Brian B; Huang, Ying; Balasenthil, Seetharaman et al. (2015) Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a Reference Set of Serum and Plasma Specimens. PLoS One 10:e0139049
Wang, Jin; Paris, Pamela L; Chen, Jinyun et al. (2015) Next generation sequencing of pancreatic cyst fluid microRNAs from low grade-benign and high grade-invasive lesions. Cancer Lett 356:404-9
Smith, Jill P; Whitcomb, David C; Matters, Gail L et al. (2015) Distribution of cholecystokinin-B receptor genotype between patients with pancreatic cancer and controls and its impact on survival. Pancreas 44:236-42
Wang, Jin; Yin, Hailin; Panandikar, Ashwini et al. (2015) Elevated cyclin A associated kinase activity promotes sensitivity of metastatic human cancer cells to DNA antimetabolite drug. Int J Oncol 47:782-90
Liu, Qian; Chen, Jinyun; Wang, Jin et al. (2014) Putative tumor suppressor gene SEL1L was downregulated by aberrantly upregulated hsa-mir-155 in human pancreatic ductal adenocarcinoma. Mol Carcinog 53:711-21
Qi, Jia-Hui; Wang, Jin; Chen, Jinyun et al. (2014) High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients. BMC Cancer 14:643
Chen, Nanyue; Balasenthil, Seetharaman; Reuther, Jacquelyn et al. (2014) DEAR1, a novel tumor suppressor that regulates cell polarity and epithelial plasticity. Cancer Res 74:5683-9

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