Concurrent mutations in ATM and genes associated with common γ chain signaling in peripheral T cell lymphoma

Haley M. Simpson, Rashid Z. Khan, Chang Song, Deva Sharma, Kavitha Sadashivaiah, Aki Furusawa, Xinyue Liu, Sushma Nagaraj, Naomi Sengamalay, Lisa Sadzewicz, Luke J. Tallon, Qing C. Chen, Ferenc Livak, Aaron P. Rapoport, Amy Kimball, Arnob Banerjee*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Article number141906
JournalPloS one
Volume10
Issue number11
DOIs
StatePublished - Nov 4 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Simpson, H. M., Khan, R. Z., Song, C., Sharma, D., Sadashivaiah, K., Furusawa, A., Liu, X., Nagaraj, S., Sengamalay, N., Sadzewicz, L., Tallon, L. J., Chen, Q. C., Livak, F., Rapoport, A. P., Kimball, A., & Banerjee, A. (2015). Concurrent mutations in ATM and genes associated with common γ chain signaling in peripheral T cell lymphoma. PloS one, 10(11), [141906]. https://doi.org/10.1371/journal.pone.0141906