Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma.

Authors :: Tiacci E
Ladewig E
Schiavoni G
Penson A
Fortini E
Pettirossi V
Wang Y
Rosseto A
Venanzi A
Vlasevska S
Pacini R
Piattoni S
Tabarrini A
Pucciarini A
Bigerna B
Santi A
Gianni AM
Viviani S
Cabras A
Ascani S
Crescenzi B
Mecucci C
Pasqualucci L
Rabadan R
Falini B
Source :: Blood [Blood] 2018 May 31; Vol. 131 (22), pp. 2454-2465. Date of Electronic Publication: 2018 Apr 12.
Publication Year :: 2018
Abstract: Dissecting the pathogenesis of classical Hodgkin lymphoma (cHL), a common cancer in young adults, remains challenging because of the rarity of tumor cells in involved tissues (usually <5%). Here, we analyzed the coding genome of cHL by microdissecting tumor and normal cells from 34 patient biopsies for a total of ∼50 000 singly isolated lymphoma cells. We uncovered several recurrently mutated genes, namely, STAT6 (32% of cases), GNA13 (24%), XPO1 (18%), and ITPKB (16%), and document the functional role of mutant STAT6 in sustaining tumor cell viability. Mutations of STAT6 genetically and functionally cooperated with disruption of SOCS1 , a JAK-STAT pathway inhibitor, to promote cHL growth. Overall, 87% of cases showed dysregulation of the JAK-STAT pathway by genetic alterations in multiple genes (also including STAT3 , STAT5B , JAK1 , JAK2 , and PTPN1 ), attesting to the pivotal role of this pathway in cHL pathogenesis and highlighting its potential as a new therapeutic target in this disease.<br /> (© 2018 by The American Society of Hematology.)