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Blood. 2016 Aug 25;128(8):1093-100. doi: 10.1182/blood-2015-12-682591. Epub 2016 Jun 20.

Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations.

Author information

1
Department of Pathology, Massachusetts General Hospital, Boston, MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;
2
Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL;
3
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York-Presbyterian Hospital, New York, NY;
4
Department of Pathology, Boston Children's Hospital, Boston, MA;
5
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA;
6
Department of Pathology, Stanford University School of Medicine, Stanford, CA;
7
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA;
8
ARUP Institute for Clinical and Experimental Pathology, Department of Pathology, University of Utah, Salt Lake City, UT;
9
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;
10
Department of Pathology, Brigham & Women's Hospital, Boston, MA;
11
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;
12
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA;
13
ARUP Laboratories, Department of Pathology, University of Utah, Salt Lake City, UT; and.
14
Department of Pathology, Massachusetts General Hospital, Boston, MA;
15
Department of Medicine, Massachusetts General Hospital, Boston, MA.
16
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA;

Abstract

Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5% of PTNFL genomes, compared with 10% of limited-stage typical FL genomes (P < .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers.

Comment in

PMID:
27325104
PMCID:
PMC5000844
DOI:
10.1182/blood-2015-12-682591
[Indexed for MEDLINE]
Free PMC Article

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