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Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors.
Vaughn, Hayley; Major, Heather; Kadera, Evangeline; Keck, Kendall; Dunham, Timothy; Qian, Qining; Brown, Bartley; Scott, Aaron; Bellizzi, Andrew M; Braun, Terry; Breheny, Patrick; Quelle, Dawn E; Howe, James R; Darbro, Benjamin.
Afiliación
  • Vaughn H; Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA.
  • Major H; Stead Family Department of Pediatrics, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Kadera E; Stead Family Department of Pediatrics, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Keck K; Stead Family Department of Pediatrics, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Dunham T; Department of Surgery, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Qian Q; Stead Family Department of Pediatrics, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Brown B; Stead Family Department of Pediatrics, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Scott A; Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA.
  • Bellizzi AM; Department of Surgery, University of Iowa Health Care, Iowa City, IA 52242, USA.
  • Braun T; Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
  • Breheny P; Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA.
  • Quelle DE; Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA.
  • Howe JR; Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA.
  • Darbro B; Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
Int J Mol Sci ; 25(14)2024 Jul 09.
Article en En | MEDLINE | ID: mdl-39062773
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 (pNETs) and 33 small-bowel neuroendocrine tumors (sbNETs). Tumors were resected from 47 early-disease-progression (<24 months) and 17 late-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 revealed 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 the primary tumor site for patients with metastatic liver NETs and to guide risk-stratified therapeutic decisions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Tumores Neuroendocrinos / Variaciones en el Número de Copia de ADN Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Tumores Neuroendocrinos / Variaciones en el Número de Copia de ADN Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza