Genetic and Clinical Characteristics of ARID1A Mutated Melanoma Reveal High Tumor Mutational Load without Implications on Patient Survival.

Autor: Thielmann CM; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Matull J; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Roth S; Department of Anesthesiology, Medical Faculty, University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany., Placke JM; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Chorti E; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Zaremba A; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Lodde G; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Jansen P; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany.; Department of Dermatology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Krefting F; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Kretz J; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Möller I; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Sucker A; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Paschen A; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Livingstone E; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Zimmer L; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Ugurel S; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Schadendorf D; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Hadaschik E; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany., Griewank KG; Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.; German Cancer Consortium (DKTK), Partner Site Essen, 45147 Essen, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Apr 22; Vol. 14 (9). Date of Electronic Publication: 2022 Apr 22.
DOI: 10.3390/cancers14092090
Abstrakt: (1) Background: Melanoma has the highest mortality of all cutaneous tumors, despite recent treatment advances. Many relevant genetic events have been identified in the last decade, including recurrent ARID1A mutations, which in various tumors have been associated with improved outcomes to immunotherapy. (2) Methods: Retrospective analysis of 116 melanoma samples harboring ARID1A mutations. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome applying Kaplan-Meier (log-rank test), Fisher's exact and Chi-squared tests. (3) Results: The majority of ARID1A mutations were in cutaneous and occult melanoma. ARID1A mutated samples had a higher number of mutations than ARID1A wild-type samples and harbored UV-mutations. A male predominance was observed. Many samples also harbored NF1 mutations. No apparent differences were noted between samples harboring genetically inactivating (frame-shift or nonsense) mutations and samples with other mutations. No differences in survival or response to immunotherapy of patients with ARID1A mutant melanoma were observed. (4) Conclusions: ARID1A mutations primarily occur in cutaneous melanomas with a higher mutation burden. In contrast to findings in other tumors, our data does not support ARID1A mutations being a biomarker of favorable response to immunotherapies in melanoma. Larger prospective studies would still be warranted.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje