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, exome and/or targeted sequencing of 26 PTNFLs (16 pediatric, 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=0.35). PTNFL was otherwise genomically bland, and specifically lacked recurrent mutations in epigenetic modifiers (e.g. CREBBP, KMT2D). Copy number aberrations (CNAs) affected a mean of only 0.5% of PTNFL genomes, compared to 10% of limited-stage typical FL genomes (p<0.02). 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 MAP kinase pathway mutations and a near absence of mutations in epigenetic modifiers.

View details for DOI 10.1182/blood-2015-12-682591

View details for PubMedID 27325104