A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells

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Gasparini , V R , Binatti , A , Coppe , A , Teramo , A , Vicenzetto , C , Calabretto , G , Barila , G , Barizza , A , Giussani , E , Facco , M , Mustjoki , S , Semenzato , G , Zambello , R & Bortoluzzi , S 2020 , ' A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells ' , Blood cancer journal , vol. 10 , no. 4 , 42 . https://doi.org/10.1038/s41408-020-0309-2

Title: A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells
Author: Gasparini, Vanessa Rebecca; Binatti, Andrea; Coppe, Alessandro; Teramo, Antonella; Vicenzetto, Cristina; Calabretto, Giulia; Barila, Gregorio; Barizza, Annica; Giussani, Edoardo; Facco, Monica; Mustjoki, Satu; Semenzato, Gianpietro; Zambello, Renato; Bortoluzzi, Stefania
Contributor organization: HUS Comprehensive Cancer Center
Department of Clinical Chemistry and Hematology
Department of Oncology
Hematologian yksikkö
University of Helsinki
TRIMM - Translational Immunology Research Program
Date: 2020-04-22
Language: eng
Number of pages: 11
Belongs to series: Blood cancer journal
ISSN: 2044-5385
DOI: https://doi.org/10.1038/s41408-020-0309-2
URI: http://hdl.handle.net/10138/315266
Abstract: The molecular pathogenesis of chronic lymphoproliferative disorder of natural killer (NK) cells (CLPD-NK) is poorly understood. Following the screening of 57 CLPD-NK patients, only five presented STAT3 mutations. WES profiling of 13 cases negative for STAT3/STAT5B mutations uncovered an average of 18 clonal, population rare and deleterious somatic variants per patient. The mutational landscape of CLPD-NK showed that most patients carry a heavy mutational burden, with major and subclonal deleterious mutations co-existing in the leukemic clone. Somatic mutations hit genes wired to cancer proliferation, survival, and migration pathways, in the first place Ras/MAPK, PI3K-AKT, in addition to JAK/STAT (PIK3R1 and PTK2). We confirmed variants with putative driver role of MAP10, MPZL1, RPS6KA1, SETD1B, TAOK2, TMEM127, and TNFRSF1A genes, and of genes linked to viral infections (DDX3X and RSF1) and DNA repair (PAXIP1). A truncating mutation of the epigenetic regulator TET2 and a variant likely abrogating PIK3R1-negative regulatory activity were validated. This study significantly furthered the view of the genes and pathways involved in CLPD-NK, indicated similarities with aggressive diseases of NK cells and detected mutated genes targetable by approved drugs, being a step forward to personalized precision medicine for CLPD-NK patients.
Subject: STAT3 MUTATIONS
GENOMIC LANDSCAPE
PATHOGENESIS
LEUKEMIA
TET2
HEMATOPOIESIS
GENETICS
DISEASE
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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