title: Concurrent Mutations in ATM and Genes Associated with Common γ Chain Signaling in Peripheral T Cell Lymphoma.
abstract: Peripheral T cell lymphoma (PTCL) is a heterogeneous malignancy with poor response to current therapeutic strategies and incompletely characterized genetics. We conducted whole exome sequencing of matched PTCL and non-malignant samples from 12 patients, spanning 8 subtypes, to identify potential oncogenic mutations in PTCL. Analysis of the mutations identified using computational algorithms, CHASM, PolyPhen2, PROVEAN, and MutationAssessor to predict the impact of these mutations on protein function and PTCL tumorigenesis, revealed 104 somatic mutations that were selected as high impact by all four algorithms. Our analysis identified recurrent somatic missense or nonsense mutations in 70 genes, 9 of which contained mutations predicted significant by all 4 algorithms: ATM, RUNX1T1, WDR17, NTRK3, TP53, TRMT12, CACNA2D1, INTS8, and KCNH8. We observed somatic mutations in ATM (ataxia telangiectasia-mutated) in 5 out of the 12 samples and mutations in the common gamma chain (γc) signaling pathway (JAK3, IL2RG, STAT5B) in 3 samples, all of which also harbored mutations in ATM. Our findings contribute insights into the genetics of PTCL and suggest a relationship between γc signaling and ATM in T cell malignancy.
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Haley M
authors.initials: HM
authors.lastname: Simpson
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Rashid Z
authors.initials: RZ
authors.lastname: Khan
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Chang
authors.initials: C
authors.lastname: Song
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Deva
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sadashivaiah
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Aki
authors.initials: A
authors.lastname: Furusawa
authors.affiliation: Genome Resource Center, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Genome Resource Center, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Sushma
authors.initials: S
authors.lastname: Nagaraj
authors.affiliation: Genome Resource Center, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sengamalay
authors.affiliation: Genome Resource Center, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sadzewicz
authors.affiliation: Genome Resource Center, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Tallon
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Qing C
authors.initials: QC
authors.lastname: Chen
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Livak
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Kimball
authors.affiliation: Program in Oncology, Greenebaum Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.|Center for Stem Cell Research and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Arnob
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000465:Algorithms; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D007142:Immunoglobulin gamma-Chains; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins