학술논문
Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression.
Document Type
Academic Journal
Author
Fléchon L; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Arib I; Department of Hematology, Lille Hospital, Lille, France.; Dutta AK; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA.; Department of Medical Oncology, Harvard Medical School, Boston, MA.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA.; Hasan Bou Issa L; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Sklavenitis-Pistofidis R; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA.; Department of Medical Oncology, Harvard Medical School, Boston, MA.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA.; Tilmont R; Department of Hematology, Lille Hospital, Lille, France.; Stewart C; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA.; Dubois R; Department of Pathology, Lille Hospital, Lille, France.; Poulain S; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Department of Hematology, Biology and Pathology Center, Lille Hospital, Lille, France.; Copin MC; Department of Pathology, Angers University, Angers Hospital, INSERM, CRCI2NA, Angers, France.; Javed S; Department of Medical Oncology, Valenciennes Hospital, Valenciennes, France.; Nudel M; Department of Hematology, Lille Hospital, Lille, France.; Cavalieri D; Department of Hematology, Lille Hospital, Lille, France.; Escure G; Department of Hematology, Lille Hospital, Lille, France.; Gower N; Department of Hematology, Lille Hospital, Lille, France.; Chauvet P; Department of Hematology, Lille Hospital, Lille, France.; Gazeau N; Department of Hematology, Lille Hospital, Lille, France.; Saade C; Department of Hematology, Lille Hospital, Lille, France.; Thiam MB; Department of Hematology, Lille Hospital, Lille, France.; Ouelkite-Oumouchal A; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Gaggero S; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Cailliau É; Department of Biostatistics, Lille Hospital, Lille, France.; Faiz S; Department of Pathology and Dermatology, Lille Hospital, Lille, France.; Carpentier O; Department of Pathology and Dermatology, Lille Hospital, Lille, France.; Duployez N; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Department of Hematology, Biology and Pathology Center, Lille Hospital, Lille, France.; Idziorek T; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Mortier L; Department of Pathology and Dermatology, Lille Hospital, Lille, France.; OncoThai unit, INSERM UMR-S1189, Lille University, Lille, France.; Figeac M; Lille University, Lille Hospital, CNRS, INSERM, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, Lille, France.; Preudhomme C; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Department of Hematology, Biology and Pathology Center, Lille Hospital, Lille, France.; Quesnel B; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Department of Hematology, Lille Hospital, Lille, France.; Mitra S; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Morschhauser F; Department of Hematology, Lille Hospital, Lille, France.; Getz G; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA.; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA.; Harvard Medical School, Boston, MA.; Ghobrial IM; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA.; Department of Medical Oncology, Harvard Medical School, Boston, MA.; Harvard Medical School, Boston, MA.; Manier S; Canther, ONCOLille, INSERM UMR-S1277, CNRS UMR9020, Lille University, Lille, France.; Department of Hematology, Lille Hospital, Lille, France.
Source
Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
Subject
Language
English
Abstract
Abstract: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.
(© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
(© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)