Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation

作者：Schmidt Janine; Enric Ramis Zaldivar Joan; Nadeu Ferran; Gonzalez Farre Blanca; Navarro Alba; Egan Caoimhe; Montes Mojarro Ivonne Aidee; Marafioti Teresa; Cabecadas Jose; van der Walt Jon; Dojcinov Stefan; Rosenwald Andreas; Ott German; Bonzheim Irina; Fend Falko; Campo Elias; Jaffe Elaine S; Salaverria Itziar; Quintanilla Martinez Leticia

来源：Blood, 2017, 130(3): 323-327.

DOI：10.1182/blood-2017-03-776278

Pediatric-type follicular lymphoma (PTFL) is a B-cell lymphoma with distinctive clinicopathological features. Recently, recurrent genetic alterations of potential importance for its pathogenesis that disrupt pathways associated with the germinal center reaction (TNFRSF14, IRF8), immune escape (TNFRSF14), and anti-apoptosis (MAP2K1) have been described. In an attempt to shed more light onto the pathogenesis of PTFL, an integrative analysis of these mutations was undertaken in a large cohort of 43 cases previously characterized by targeted next-generation sequencing and copy number array. Mutations in MAP2K1 were found in 49% (20/41) of the cases, second in frequency to TNFRSF14 alterations (22/41; 54%), and all together were present in 81% of the cases. Immunohistochemical analysis of the MAP2K1 downstream target extracellular signal-regulated kinase demonstrated its phosphorylation in the evaluable cases and revealed a good correlation with the allelic frequency of the MAP2K1 mutation. The IRF8p.K66R mutation was present in 15%(6/39) of the cases and was concomitant with TNFRSF14 mutations in 4 cases. This hot spot seems to be highly characteristic for PTFL. In conclusion, TNFRSF14 and MAP2K1 mutations are the most frequent genetic alterations found in PTFL and occur independently inmost cases, suggesting that both mutations might play an important role in PTFL lymphomagenesis.

• 出版日期2017-7-20