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Oncogenic pathway signatures predict the risk of progression and recurrence in well-differentiated pancreatic neuroendocrine tumors.

Authors :
Mederos MA
Court CM
Dipardo BJ
Pisegna JR
Dawson DW
Joe Hines O
Donahue TR
Graeber TG
Girgis MD
Tomlinson JS
Source :
Journal of surgical oncology [J Surg Oncol] 2024 Oct; Vol. 130 (5), pp. 1070-1077. Date of Electronic Publication: 2024 Aug 19.
Publication Year :
2024

Abstract

Background: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS).<br />Methods: Whole-exome sequencing of resected well-differentiated, low and intermediate-grade (G1 and G2) pNETs and normal adjacent tissue from patients who underwent resection from 2005 to 2015 was performed. Genetic alterations were classified using pan-genomic and oncogenic pathway classifications. Additional samples with genetic and clinicopathologic data available were obtained from the publicly available International Cancer Genome Consortium (ICGC) database and included in the analysis. The prognostic relevance of these genomic signatures on PFS and RFS was analyzed.<br />Results: Thirty-one patients who underwent resection for pNET were identified. Genomic analysis of mutational, copy number, cytogenetic, and complex phenomena revealed similar patterns to prior studies of pNETs with relatively few somatic gene mutations but numerous instances of copy number changes. Analysis of genomic and clinicopathologic outcomes using the combined data from our study as well as the ICGC pNET cohort (n = 124 patients) revealed that the recurrent pattern of whole chromosome loss (RPCL) and metastatic disease were independently associated with disease progression. When evaluating patients with local disease at the time of resection, RPCL and alterations in the TGFβ oncogenic pathway were independently associated with the risk of recurrence.<br />Conclusions: Well-differentiated pNETs are genomically diverse tumors. Pathway signatures may be prognostic for predicting disease progression and recurrence.<br /> (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1096-9098
Volume :
130
Issue :
5
Database :
MEDLINE
Journal :
Journal of surgical oncology
Publication Type :
Academic Journal
Accession number :
39155697
Full Text :
https://doi.org/10.1002/jso.27830