Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
09 02 2021
09 02 2021
Historique:
received:
01
06
2020
accepted:
20
11
2020
entrez:
9
2
2021
pubmed:
10
2
2021
medline:
29
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33560380
pii: S2473-9529(21)00092-6
doi: 10.1182/bloodadvances.2020002469
pmc: PMC7876877
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
649-661Subventions
Organisme : NCI NIH HHS
ID : K08 CA191019
Pays : United States
Organisme : NIAID NIH HHS
ID : DP2 AI136599
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001424
Pays : United States
Organisme : NCI NIH HHS
ID : K23 CA184279
Pays : United States
Organisme : Doris Duke Charitable Foundation
ID : 2016095
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM011271
Pays : United States
Informations de copyright
© 2021 by The American Society of Hematology.
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