Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient.
Publication/Presentation Date
7-1-2012
Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is rarely a survivable disease. In rare cases, separate synchronous tumors are discovered at the time of resection, while in others, patients present with a metachronous cancer after prior surgical resection. Studying molecular markers of synchronous and metachronous lesions may aid to clarify the biology of this often deadly disease.
METHODS: Two patients presented with synchronous tumors (each one with a tumor in the pancreatic head/neck and the other in the tail, designated patients A and B). An additional patient (patient C) underwent an R0 resection for PDA of the head and recurred 1.5 y later with PDA in the tail. Genomic DNA was laser capture microdissected (LCM) from the tumor and molecular analysis was performed. K-ras status and loss of heterozygosity (LOH) were determined from multiple specimens for each case.
RESULTS: All samples from each patient harbored identical K-ras mutations. In patient A, the tumor at the head of the pancreas had more clonal genetic instability as reflected by LOH analysis over multiple LCM samples. Patient B had more genetic instability in the tail lesion compared with the neck. Patient C had virtually the identical molecular profile in both tumors, supporting the notion that both tumors were related.
CONCLUSION: We conclude that the synchronous and metachronous tumors likely are initiated from identical precursor lesions and/or events (i.e., K-ras mutations). Future studies will need to investigate if these tumors will respond similarly to adjuvant therapies targeted against the clonal molecular events in the tumor.
Volume
176
Issue
1
First Page
154
Last Page
158
ISSN
1095-8673
Published In/Presented At
Talbott, V. A., Yeo, C. J., Brody, J. R., & Witkiewicz, A. K. (2012). Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient. The Journal of surgical research, 176(1), 154–158. https://doi.org/10.1016/j.jss.2011.09.043
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
22118834
Department(s)
Administration and Leadership
Document Type
Article