The molecular genetic changes of human pancreatic carcinoma are largely unknown but there is compelling evidence that undiscovered tumor suppressor genes are involved. Tumor suppressor genes are found frequently at sites of genetic less in human cancers. Two molecular genetic techniques have been shown to identify areas of genetic loss in carcinoma: allelotyping of polymorphic markers and representational difference analysis (RDA). This proposal aims to use these methods to further study the phenomenon of genetic loss in human carcinomas, to identify new tumor suppressor genes from areas of homozygous genomic deletion, and to characterize the genetic changes in pre-invasive precursor lesions of pancreatic carcinoma. Preliminary studies are provided for all aspects of this proposal. Drs. Leland Chung and joyce Hamlin will co-mentor the applicant; both have trained numerous graduate students and post-doctoral fellows, and have a long history of NIH grant support. Dr Hamlin is a Professor in the Dept. of Biochemistry, with an expertise in molecular genetic analysis of eukaryotic genomes. Dr. Chung is a Professor in the Dept. of Urology, with an expertise in cellular biology of human cancer. Together they provide the requisite experience in cancer biology and molecular genetic methodology to guide the applicant through the proposed research project and will aid the applicant in obtaining continuing finding during the later stages of this proposal. The applicant has secured a position of Asst. Professor in the Dept. of Pathology at the University of Virginia, which has committed lab space, funds for equipment and supplies, and technical support. The University of Virginia Hospital has an extensive frozen tumor bank and tissue procural procedures in place to support the research proposal. The applicant has shown competence in the field of molecular biology by publishing four first author peer-reviewed publications on DNA-protein interactions during his Ph,D training at Duke University. He has continued in scholarly pursuits during his subsequent clinical training at the National Institutes of Health and fellowship training at The Johns Hopkins University School of Medicine, with several abstracts and publications in diagnostic pathology and basic research. His long term goals are to establish himself as an independent investigator in the genetic basis of human carcinogenesis. The environment at The University of Virginia provides him with seminar series and participation in scientific journal clubs to remain current in the scientific literature, and forums for the presentation of his ongoing research for critical appraisal. Thr proposed project will establish for the applicant an independent research program and will provide him the training in personnel supervision and grant application that re necessary for a successful career in cancer research.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA074431-02
Application #
2517797
Study Section
Cancer Research Manpower and Education Review Committee (CRME)
Project Start
1996-09-01
Project End
2001-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Virginia
Department
Pathology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Rutherford, Sue; Yu, Yongtao; Rumpel, Craig A et al. (2006) Chromosome 6 deletion and candidate tumor suppressor genes in adenoid cystic carcinoma. Cancer Lett 236:309-17
Patel, Shetal A; Adams, Reid; Goldstein, Meryl et al. (2002) Genetic analysis of invasive carcinoma arising in intraductal oncocytic papillary neoplasm of the pancreas. Am J Surg Pathol 26:1071-7
El-Rifai, W; Rutherford, S; Knuutila, S et al. (2001) Novel DNA copy number losses in chromosome 12q12--q13 in adenoid cystic carcinoma. Neoplasia 3:173-8
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Moskaluk, C A; Tian, Q; Marshall, C R et al. (1999) Mutations of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors. Oncogene 18:1897-902
Cerilli, L A; Swartzbaugh, J R; Saadut, R et al. (1999) Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas. Hum Pathol 30:1242-6
Rumpel, C A; Powell, S M; Moskaluk, C A (1999) Mapping of genetic deletions on the long arm of chromosome 4 in human esophageal adenocarcinomas. Am J Pathol 154:1329-34
Moskaluk, C A; Rumpel, C A (1998) Allelic deletion in 11p15 is a common occurrence in esophageal and gastric adenocarcinoma. Cancer 83:232-9
Moskaluk, C A; Hu, J; Perlman, E J (1998) Comparative genomic hybridization of esophageal and gastroesophageal adenocarcinomas shows consensus areas of DNA gain and loss. Genes Chromosomes Cancer 22:305-11
Moskaluk, C A; Kern, S E (1997) Microdissection and polymerase chain reaction amplification of genomic DNA from histological tissue sections. Am J Pathol 150:1547-52

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