| Literature DB >> 29650799 |
Enrico Tiacci1, Erik Ladewig2, Gianluca Schiavoni1, Alex Penson2, Elisabetta Fortini1, Valentina Pettirossi1, Yuchun Wang1, Ariele Rosseto1, Alessandra Venanzi1, Sofija Vlasevska3, Roberta Pacini1, Simonetta Piattoni1, Alessia Tabarrini1, Alessandra Pucciarini1, Barbara Bigerna1, Alessia Santi1, Alessandro M Gianni4, Simonetta Viviani4, Antonello Cabras5, Stefano Ascani1, Barbara Crescenzi1, Cristina Mecucci1, Laura Pasqualucci3, Raul Rabadan2, Brunangelo Falini1.
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.Entities:
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Year: 2018 PMID： 29650799 PMCID： PMC6634958 DOI： 10.1182/blood-2017-11-814913
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113