Ignite Creation Date:
2024-05-05 @ 10:26 PM
Last Modification Date:
2024-10-26 @ 10:18 AM
Study NCT ID:
NCT01103128
Status:
TERMINATED
Last Update Posted:
2015-06-23
First Post:
2010-04-12
Brief Title:
Validation of a Mouse Model of Pancreatic Carcinogenesis
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
BRCA1 and BRCA2 Genetic Mutations in Mucinous Versus Nonmucinous Precursor Lesions of the Pancreas Validation of a Mouse Model of Pancreatic Carcinogenesis
Status:
TERMINATED
Status Verified Date:
2012-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 BRCA12 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
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
Detailed Description:
Pancreatic ductal adenocarcinoma PDAC is the fourth leading cause of death from malignancy in the United States Several gene mutations and cancer syndromes have been identified that are found in greater frequency in individuals with PDAC including the breast ovary cancer syndrome BRCA1 and BRCA2 mutations We have recently generated mouse models of pancreatic cancer in which we found that deletions of either BRCA1 or BRCA2 cooperate with K-ras activation and p53 mutations to increase the rate of tumorigenesis via accelerated progression of Pancreatic Intraepithelial Neoplasia PanIN However only BRCA1 deletions were associated with the development of concomitant Mucinous Cystic Neoplasms MCNs suggesting potentially distinct pathways for BRCA1- and BRCA2-mediated tumorigenesis in the pancreas Our primary aim is to determine if germline mutations of BRCA1 and BRCA2 result in different pre-neoplastic pathways to pancreatic cancer as 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 Our secondary aim is to evaluate the interaction of p53 and Kras with BRCA1 and BRCA2 by sequencing p53 and Kras in PanIN as compared to IPMN and MCN lesions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| AAAE0097 | OTHER | Columbia University IRB | None |