دورية أكاديمية
Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.
| العنوان: | Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics. |
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| المؤلفون: | Kohlmann W; University of Utah Huntsman Cancer Institute, Salt Lake City, UT.; VA Medical Center, National TeleOncology, Clinical Cancer Genetics Service, Durham, NC., Nix DA; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Pauley K; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Greenberg S; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Atkinson A; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Boucher KM; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Kolesar J; University of Kentucky, Lexington, KY., Singer EA; Rutgers Cancer Institute of New Jersey, Newark, NJ.; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Edge SB; Roswell Park Comprehensive Cancer Center, Buffalo, NY., Churchman ML; Aster Insights, Hudson, FL., Graham L; University of Colorado Cancer Center, Aurora, CO., Salhia B; Department of Translational Genomics, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA., Sanchez A; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Zakharia Y; University of Iowa's Holden Comprehensive Cancer Center, Iowa City, IA., Nepple KG; University of Iowa's Holden Comprehensive Cancer Center, Iowa City, IA., Schneider BP; University of Iowa's Holden Comprehensive Cancer Center, Iowa City, IA., Byrne L; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Jain RK; Moffitt Cancer Center, Tampa, FL., Chahoud J; Moffitt Cancer Center, Tampa, FL., Feng BJ; University of Utah Huntsman Cancer Institute, Salt Lake City, UT.; University of Utah Department of Dermatology, Salt Lake City, UT., Gupta S; University of Utah Huntsman Cancer Institute, Salt Lake City, UT.; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT. |
| المصدر: | JCO precision oncology [JCO Precis Oncol] 2024 Jun; Vol. 8, pp. e2300697. |
| نوع المنشور: | Journal Article; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 101705370 Publication Model: Print Cited Medium: Internet ISSN: 2473-4284 (Electronic) Linking ISSN: 24734284 NLM ISO Abbreviation: JCO Precis Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Alexandria, VA : American Society of Clinical Oncology, [2017]- |
| مواضيع طبية MeSH: | Germ-Line Mutation* , Exome Sequencing* , Urologic Neoplasms*/genetics, Humans ; Male ; Female ; Middle Aged ; Aged ; Genomics ; Genetic Predisposition to Disease ; Adult ; Aged, 80 and over ; Cohort Studies |
| مستخلص: | Purpose: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). Methods: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. Results: Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease ( P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without ( P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. Conclusion: Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra. |
| معلومات مُعتمدة: | I01 BX005765 United States BX BLRD VA |
| تواريخ الأحداث: | Date Created: 20240708 Date Completed: 20240708 Latest Revision: 20240814 |
| رمز التحديث: | 20240814 |
| DOI: | 10.1200/PO.23.00697 |
| PMID: | 38976819 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2473-4284 |
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| DOI: | 10.1200/PO.23.00697 |