Details

Autor(en) / Beteiligte

• Louissaint, Abner
• Schafernak, Kristian T.
• Geyer, Julia T.
• Kovach, Alexandra E.
• Ghandi, Mahmoud
• Gratzinger, Dita
• Roth, Christine G.
• Paxton, Christian N.
• Kim, Sunhee
• Namgyal, Chungdak
• Morin, Ryan
• Morgan, Elizabeth A.
• Neuberg, Donna S.
• South, Sarah T.
• Harris, Marian H.
• Hasserjian, Robert P.
• Hochberg, Ephraim P.
• Garraway, Levi A.
• Harris, Nancy Lee
• Weinstock, David M.

Titel

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

Ist Teil von

• Blood, 2016-08, Vol.128 (8), p.1093-1100

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. •PTNFL is a biologically distinct indolent lymphoma characterized by common MEK/ERK pathway mutations.•The biology of PTNFL is not defined by age, as the mutational profile is similar in pediatric and adult cases.