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Blood. 2018 May 31;131(22):2454-2465. doi: 10.1182/blood-2017-11-814913. Epub 2018 Apr 12.

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

Author information

1
Institute of Hematology and Center for Hemato-Oncology Research, University and Hospital of Perugia, Perugia, Italy.
2
Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, NY.
3
Institute for Cancer Genetics and the Department of Pathology and Cell Biology, Columbia University, New York, NY.
4
Medical Oncology and.
5
Anatomic Pathology, National Cancer Institute, Milan, Italy.

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.

PMID:
29650799
PMCID:
PMC6634958
DOI:
10.1182/blood-2017-11-814913
[Indexed for MEDLINE]
Free PMC Article

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