Genetic profiling of melanoma in routine diagnostics

• Verfasst von: Leichsenring, Jonas [VerfasserIn]
• Verfasst von: Stögbauer, Fabian [VerfasserIn]
• Verfasst von: Volckmar, Anna-Lena [VerfasserIn]
• Verfasst von: Kirchner, Martina [VerfasserIn]
• Verfasst von: Fröhling, Stefan [VerfasserIn]
• Verfasst von: Hassel, Jessica C. [VerfasserIn]
• Verfasst von: Enk, Alexander [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Endris, Volker [VerfasserIn]
• Verfasst von: Penzel, Roland [VerfasserIn]
• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Titel: Genetic profiling of melanoma in routine diagnostics
• Titelzusatz: assay performance and molecular characteristics in a consecutive series of 274 cases
• Verf.angabe: Jonas Leichsenring, Fabian Stögbauer, Anna-Lena Volckmar, Ivo Buchhalter, Cristiano Oliveira, Martina Kirchner, Stefan Fröhling, Jessica Hassel, Alexander Enk, Peter Schirmacher, Volker Endris, Roland Penzel, Albrecht Stenzinger
• E-Jahr: 2018
• Jahr: 20 October 2018
• Umfang: 8 S.
• Fussnoten: Gesehen am 26.02.2020
• Titel Quelle: Enthalten in: Pathology
• Ort Quelle: Amsterdam : Elsevier, 1969
• Jahr Quelle: 2018
• Band/Heft Quelle: 50(2018), 7, Seite 703-710
• ISSN Quelle: 1465-3931
• DOI: doi:10.1016/j.pathol.2018.08.004
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: BRAF
• Sach-SW: Melanoma
• Sach-SW: molecular diagnostics
• Sach-SW: NRAS
• Sach-SW: triple wild type
• K10plus-PPN: 1691040460

Abstract

A deeper understanding of melanoma biology has opened up new avenues for mechanistically informed therapies. However, data on the prevalence of druggable genetic lesions in melanoma are still conflicting and real-world performance data on high-throughput genetic profiling of melanoma cases using formalin fixed, paraffin embedded (FFPE) tissue with variable tumour cellularity and quality are lacking. We retrospectively analysed targeted next-generation sequencing data of 274 consecutive melanoma samples obtained for routine diagnostics between December 2013 and July 2017. Actionable mutations were detected in 197 cases (71.9%), of which activating BRAF (mostly p.V600E/K) and RAS (mostly p.Q61R/K) mutations occurred in 40.5% (n = 111) and 30.3% (n = 83) of cases, respectively. We identified driver mutations of the Triple-WT subgroup in 10.6% of cases (n = 29; 10 with activating KIT mutations). Median turnaround time was 5 working days with no dropouts. Tumour cellularity ranged from 5% to 95% and successful sequencing was possible at DNA concentrations as low as 0.03 ng/μL (median 10.58 ng/μL; range 0.03-209.05 ng/μL). Fast, quality-controlled high-throughput genetic profiling of FFPE melanoma samples is feasible and provides a landscape of genetic aberrations in melanoma that is currently relevant in clinical practice and approximates TCGA subtypes.