Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma.

Autor: Katims AB; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Gaffney C; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Firouzi S; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Yip W; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Aulitzky A; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Pietzak EJ; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Donat SM; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Bochner BH; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Donahue TF; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Herr HW; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Dalbagni G; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Al-Ahmadie H; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Kim K; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Solit DB; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY., Lin O; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Coleman JA; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: colemanj@mskcc.org.
Jazyk: angličtina
Zdroj: Urologic oncology [Urol Oncol] 2023 Oct; Vol. 41 (10), pp. 433.e19-433.e24. Date of Electronic Publication: 2023 Aug 26.
DOI: 10.1016/j.urolonc.2023.07.007
Abstrakt: Background: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor.
Methods: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated).
Results: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue.
Conclusions: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.
Competing Interests: Declaration of Competing Interest Andrew B. Katims certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matters or materials discussed in the manuscripts (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Wesley Yip serves as a consultant/advisor to Gilead. Eugene J. Pietzak serves as a consultant/advisor to Merck, Chugai Pharma, QED Therapeutics, Janssen, and Urogen Pharma. Bernard H. Bochner serves as a consultant/advisor to Olympus. Hikmat Al-Ahmadie serves as a consultant/advisor to AstraZeneca/MedImmune, Janssen, and PAIGE.AI. David B. Solit serves as a consultant/advisor to Pfizer, Loxo/Lilly Oncology, Vividon Therapeutics, Scorpion Therapeutics, Fore Therapeutics, FOG Pharma, Rain Therapeutics, and BridgeBio. Jonathan A. Coleman has uncompensated cooperative research agreements with AngioDynamics and Metabolon. None of these companies contributed to or directed any of the research reported in this article. The other authors (Andrew B. Katims, Christopher Gaffney, Sanaz Firouzi, Andreas Aulitzky, S. Machele Donat, Timothy F. Donahue, Harry W. Herr, Guido Dalbagni, Kwanghee Kim, and Oscar Lin) declare that they have no competing interests.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: