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