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Blood Cancer J. 2018 Jan 19;8(1):11. doi: 10.1038/s41408-017-0036-5.

SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia.

Author information

1
Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. patricia.johansson@uk-essen.de.
2
Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany. patricia.johansson@uk-essen.de.
3
Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
4
Lead Discovery Center GmbH, Dortmund, Germany.
5
Center for Drug Discovery, Department of Pediatrics, Emory Center for AIDS Research, Emory University, Children's Healthcare of Atlanta, Atlanta, GA, USA.
6
Institute for Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig Holstein, Kiel, Germany.
7
Institute of Human Genetics, University of Ulm and University Hospital of Ulm, Ulm, Germany.
8
Department of Molecular Therapy in Haematology and Oncology, National Center for Tumor Diseases and German Cancer Research Center, Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
9
German Cancer Consortium (DKTK), Heidelberg, Germany.
10
Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Abstract

T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated. We identified recurrently mutated genes previously unknown to be mutated in T-PLL, which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1. SAMHD1 regulates cellular deoxynucleotide levels and acts as a potential tumor suppressor in other leukemias. We observed destructive mutations in 18% of cases as well as deletions in two further cases. Taken together, we identified additional genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, and HERC2) as being recurrently mutated in T-PLL. Thus, our study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.

PMID:
29352181
PMCID:
PMC5802577
DOI:
10.1038/s41408-017-0036-5
[Indexed for MEDLINE]
Free PMC Article

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