Vaughn, H.; Major, H.; Kadera, E.; Keck, K.; Dunham, T.; Qian, Q.; Brown, B.; Scott, A.; Bellizzi, A.M.; Braun, T.; Breheny, P.; Quelle, D.E.; Howe, J.R.; Darbro, B. Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors. Int. J. Mol. Sci.2024, 25, 7532.
Vaughn, H.; Major, H.; Kadera, E.; Keck, K.; Dunham, T.; Qian, Q.; Brown, B.; Scott, A.; Bellizzi, A.M.; Braun, T.; Breheny, P.; Quelle, D.E.; Howe, J.R.; Darbro, B. Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors. Int. J. Mol. Sci. 2024, 25, 7532.
Vaughn, H.; Major, H.; Kadera, E.; Keck, K.; Dunham, T.; Qian, Q.; Brown, B.; Scott, A.; Bellizzi, A.M.; Braun, T.; Breheny, P.; Quelle, D.E.; Howe, J.R.; Darbro, B. Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors. Int. J. Mol. Sci.2024, 25, 7532.
Vaughn, H.; Major, H.; Kadera, E.; Keck, K.; Dunham, T.; Qian, Q.; Brown, B.; Scott, A.; Bellizzi, A.M.; Braun, T.; Breheny, P.; Quelle, D.E.; Howe, J.R.; Darbro, B. Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors. Int. J. Mol. Sci. 2024, 25, 7532.
Abstract
Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.
Keywords
Neuroendocrine tumors; functional copy number alterations; fluorescence in situ hybridization; diagnostic biomarkers; risk-stratifying biomarkers
Subject
Biology and Life Sciences, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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