TY - JOUR
T1 - Concurrent mutations in ATM and genes associated with common γ chain signaling in peripheral T cell lymphoma
AU - Simpson, Haley M.
AU - Khan, Rashid Z.
AU - Song, Chang
AU - Sharma, Deva
AU - Sadashivaiah, Kavitha
AU - Furusawa, Aki
AU - Liu, Xinyue
AU - Nagaraj, Sushma
AU - Sengamalay, Naomi
AU - Sadzewicz, Lisa
AU - Tallon, Luke J.
AU - Chen, Qing C.
AU - Livak, Ferenc
AU - Rapoport, Aaron P.
AU - Kimball, Amy
AU - Banerjee, Arnob
N1 - Funding Information:
This work was supported by National Institute of Health grants (P30CA134272, K08HL93207), the Gabrielle’s Angel Foundation for Cancer Research, the American Cancer Society and the Marlene and Stewart Greenebaum Cancer Center. Cell sorting was performed at the Marlene and Stewart Greenebaum Cancer Center Flow Cytomerty Shared Service.
Publisher Copyright:
© 2015 Simpson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/11/4
Y1 - 2015/11/4
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0141906
DO - 10.1371/journal.pone.0141906
M3 - Article
C2 - 26536348
AN - SCOPUS:84951134765
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 11
M1 - 141906
ER -