Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features.

Autor:	Zhou XA; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL., Yang J; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL., Ringbloom KG; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL., Martinez-Escala ME; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL., Stevenson KE; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA., Wenzel AT; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL., Fantini D; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.; Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL., Martin HK; Department of Pathology, Massachusetts General Hospital, Boston, MA., Moy AP; Department of Pathology, Massachusetts General Hospital, Boston, MA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Morgan EA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Harkins S; Department of Pathology, Massachusetts General Hospital, Boston, MA., Paxton CN; Associated Regional and University Pathologists, Inc (ARUP) Institute for Clinical and Experimental Pathology, Salt Lake City, UT., Hong B; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT., Andersen EF; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT., Guitart J; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL., Weinstock DM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.; Broad Institute, Harvard and Massachusetts Institute of Technology, Cambridge, MA; and., Cerroni L; Department of Dermatology, Medical University of Graz, Graz, Austria., Choi J; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL., Louissaint A; Department of Pathology, Massachusetts General Hospital, Boston, MA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2021 Feb 09; Vol. 5 (3), pp. 649-661.
DOI:	10.1182/bloodadvances.2020002469
Abstrakt:	Primary cutaneous follicle center lymphomas (PCFCLs) are indolent B-cell lymphomas that predominantly remain skin restricted and manageable with skin-directed therapy. Conversely, secondary cutaneous involvement by usual systemic follicular lymphoma (secondary cutaneous follicular lymphoma [SCFL]) has a worse prognosis and often necessitates systemic therapy. Unfortunately, no histopathologic or genetic features reliably differentiate PCFCL from SCFL at diagnosis. Imaging may miss low-burden internal disease in some cases of SCFLs, leading to misclassification as PCFCL. Whereas usual systemic FL is well characterized genetically, the genomic landscapes of PCFCL and SCFL are unknown. Herein, we analyzed clinicopathologic and immunophenotypic data from 30 cases of PCFCL and 10 of SCFL and performed whole-exome sequencing on 18 specimens of PCFCL and 6 of SCFL. During a median follow-up of 7 years, 26 (87%) of the PCFCLs remained skin restricted. In the remaining 4 cases, systemic disease developed within 3 years of diagnosis. Although the SCFLs universally expressed BCL2 and had BCL2 rearrangements, 73% of the PCFCLs lacked BCL2 expression, and only 8% of skin-restricted PCFCLs had BCL2 rearrangements. SCFLs showed low proliferation fractions, whereas 75% of PCFCLs had proliferation fractions >30%. Of the SCFLs, 67% had characteristic loss-of-function CREBBP or KMT2D mutations vs none in skin-restricted PCFCL. Both SCFL and skin-restricted PCFCL showed frequent TNFRSF14 loss-of-function mutations and copy number loss at chromosome 1p36. These data together establish PCFCL as a unique entity with biological features distinct from usual systemic FL and SCFL. We propose 3 criteria based on BCL2 rearrangement, chromatin-modifying gene mutations (CREBBP, KMT2D, EZH2, and EP300), and proliferation index to classify cutaneous FL specimens based on the likelihood of concurrent or future systemic spread. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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