Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma.

Autor: Lorenzi L; Pathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia. luisa.lorenzi@unibs.it., Haferlach T; MLL Munich Leukemia Laboratory, Munich., Mori L; Laboratory of Molecular Medicine, Department of Clinical and Experimental Science, University of Brescia, Brescia., Simbeni M; Pathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia., Walter W; MLL Munich Leukemia Laboratory, Munich., Balzarini P; Pathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia., Meggendorfer M; MLL Munich Leukemia Laboratory, Munich., Döring C; Dr Senckenberg Institute of Pathology, Goethe University, Frankfurt., Lonardi S; Pathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia., Bugatti M; Pathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia., Agostinelli C; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy'., Mehta J; Neuberg Oncopath, Mumbai, India., Borges A; Histopathology, SRL Diagnostics, Mumbai, India., Agaimy A; Institute of Pathology, University Hospital, Erlangen., Simonitsch-Klupp I; Institute of Pathology, Medical University of Vienna, Vienna, Austria., Cabeçadas J; Department of Pathology, Portuguese Institute of Oncology, Lisbon, Portugal., Campo E; Hematopathology Section, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain., Pileri SA; Division of Haematopathology, European Institute of Oncology (IEO) IRCCS, Milan., Facchetti F; Pathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia., Leo Hansmann M; Institute for General Pharmacology and Toxicology, Goethe University, Frankfurt., Hartmann S; Dr Senckenberg Institute of Pathology, Goethe University, Frankfurt.
Jazyk: angličtina
Zdroj: Haematologica [Haematologica] 2024 Jun 01; Vol. 109 (6), pp. 1815-1824. Date of Electronic Publication: 2024 Jun 01.
DOI: 10.3324/haematol.2023.283669
Abstrakt: Standardized treatment options are lacking for patients with unresectable or multifocal follicular dendritic cell sarcoma (FDCS) and disease-related mortality is as high as 20%. Applying whole-genome sequencing (WGS) in one case and whole-exome sequencing (WES) in additional twelve cases, this study adds information on the molecular landscape of FDCS, expanding knowledge on pathobiological mechanisms and identifying novel markers of potential theragnostic significance. Massive parallel sequencing showed high frequency of mutations on oncosuppressor genes, particularly in RB1, CARS and BRCA2 and unveiled alterations on homologous recombination DNA damage repair-related genes in 70% (9/13) of cases. This indicates that patients with high-stage FDCS may be eligible for poly ADP ribose polymerase inhibition protocols. Low tumor mutational burden was confirmed in this study despite common PDL1 expression in FDCS arguing on the efficacy of immune checkpoint inhibitors. CDKN2A deletion, detected by WGS and confirmed by fluorescence in situ hybridization in 41% of cases (9/22) indicates that impairment of cell cycle regulation may sustain oncogenesis in FDCS. Absence of mutations in the RAS/RAF/MAPK pathway and lack of clonal hematopoiesis-related mutations in FDCS sanction its differences from dendritic cell-derived neoplasms of hematopoietic derivation. WGS and WES in FDCS provides additional information on the molecular landscape of this rare tumor, proposing novel candidate genes for innovative therapeutical approaches to improve survival of patients with multifocal disease.
Databáze: MEDLINE
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