Validation of a Mouse Model of Pancreatic Carcinogenesis

NCT01103128 | Terminated DMC

• 1 other identifier: AAAE0097
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this study is to determine if mutations of BRCA1 and BRCA2 result in different precancerous pathways to pancreatic ductal adenocarcinoma (PDAC), as suggested in our validated mouse model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for PDAC, intraductal papillary mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN). Tissue will be examined for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be examined to look for mutations in the other BRCA1 or BRCA2 allele. The interaction between other cancer causing genes with BRCA1/2 will also be evaluated by comparing the sequences of the other genes in pre-cancerous lesions. We hypothesize that BRCA1- and BRCA2-mediated pancreatic ductal adenocarcinoma progresses through the PanIN route, as seen in both BRCA1 and BRCA2 murine models of pancreatic cancer. We further hypothesize that BRCA1 mutations may enable an additional pre- neoplastic pathway through MCN, and that IPMN may embody yet another pre- neoplastic pathway.

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer; Pre-neoplastic lesions; Breast and Ovarian Cancer Syndrome; BRCA1/2; Mouse model for pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• BRCA1 vs. BRCA2 mutations

  The primary aim is to determine if germline mutations of BRCA1 and BRCA2 result in different pre-neoplastic pathways to pancreatic cancer, as seen in our murine model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for pancreatic cancer, IPMN or MCN. Tissue will be genotyped for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be microdissected to look for loss of heterozygosity at the BRCA1 or BRCA2 allele.

  1 year

Secondary Outcomes (1)

• Interaction of other cancer genes with BRCA1 and BRCA2

  1 year

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All subjects have a tissue-confirmed diagnosis of pancreatic adenocarcinoma, MCN or IPMN and underwent surgical resection for pancreatic adenocarcinoma, MCN or IPMN at Columbia-Presbyterian Medical Center.

You may qualify if:

• Tissue-confirmed diagnosis of pancreatic adenocarcinoma, MCN, or IPMN.
• Underwent surgical resection for pancreatic adenocarcinoma, MCN, or IPMN.

You may not qualify if:

• Unwilling to provide informed consent.
• Under the age of 18.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

* Peripheral Blood Specimens: Three tubes of blood will be collected from each study participant. Two tubes will be EDTA-whole blood and one tube will be serum. Each tube will contain \~4-5 ml. A portion of the blood will be utilized to extract white blood cells that will be immortalized by EBV infection. * Archived Fixed Tissue Samples: Tissue blocks from surgery performed at CUMC or elsewhere, will be requested after obtaining consent for study participation. * Fresh Tissue Collection: At the time of surgery for tumor resection, tumor and adjacent normal tissue will be requested from the Pathology Department. At the time of endoscopy, aspirated fluid or biopsied tissue will be requested. No additional tissue will be resected beyond that required for surgical or endoscopic management. * Genetic Testing: All genetic testing will be performed in a research laboratory. Test results from research laboratories will not be disclosed to patients.

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Wendy K Chung, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics, Molecular Genetics

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 14, 2010
• Study Start: March 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 23, 2015

Record last verified: 2012-07

Locations

US (1)