Open Access

A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis

  • Authors:
    • Alexandra Butzmann
    • Kaushik Sridhar
    • Diwash Jangam
    • Jyoti Kumar
    • Malaya Kumar Sahoo
    • Nahid Shahmarvand
    • Roger Warnke
    • Elumalai Rangasamy
    • Benjamin Alan Pinsky
    • Robert Shigeo Ohgami
  • View Affiliations

  • Published online on: July 28, 2020     https://doi.org/10.3892/ijmm.2020.4686
  • Pages: 1466-1476
  • Copyright: © Butzmann et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angioimmunoblastic T‑cell lymphoma (AITL) is a uniquely aggressive mature T‑cell neoplasm. In recent years, recurrent genetic mutations in ras homolog family member A (RHOA), tet methylcytosine dioxygenase 2 (TET2), DNA methyltransferase 3 alpha (DNMT3A) and isocitrate dehydrogenase [NADP(+)] 2 (IDH2) have been identified as associated with AITL. However, a deep molecular study assessing both DNA mutations and RNA expression profile combined with digital image analysis is lacking. The present study aimed to evaluate the significance of molecular and morphologic features by high resolution digital image analysis in several cases of AITL. To do so, a total of 18 separate tissues from 10 patients with AITL were collected and analyzed. The results identified recurrent mutations in RHOA, TET2, DNMT3A, and IDH2, and demonstrated increased DNA mutations in coding, promoter and CCCTC binding factor (CTCF) binding sites in RHOA mutated AITLs vs. RHOA non‑mutated cases, as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed that RHOA mutated cells have decreased eccentricity (more circular) compared with RHOA non‑mutated AITL cells. In conclusion, the results from the present study expand our understanding of AITL and demonstrate that there are specific cell biological and morphological manifestations of RHOA mutations in cases of AITL.
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October-2020
Volume 46 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Butzmann A, Sridhar K, Jangam D, Kumar J, Sahoo MK, Shahmarvand N, Warnke R, Rangasamy E, Pinsky BA, Ohgami RS, Ohgami RS, et al: A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis. Int J Mol Med 46: 1466-1476, 2020.
APA
Butzmann, A., Sridhar, K., Jangam, D., Kumar, J., Sahoo, M.K., Shahmarvand, N. ... Ohgami, R.S. (2020). A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis. International Journal of Molecular Medicine, 46, 1466-1476. https://doi.org/10.3892/ijmm.2020.4686
MLA
Butzmann, A., Sridhar, K., Jangam, D., Kumar, J., Sahoo, M. K., Shahmarvand, N., Warnke, R., Rangasamy, E., Pinsky, B. A., Ohgami, R. S."A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis". International Journal of Molecular Medicine 46.4 (2020): 1466-1476.
Chicago
Butzmann, A., Sridhar, K., Jangam, D., Kumar, J., Sahoo, M. K., Shahmarvand, N., Warnke, R., Rangasamy, E., Pinsky, B. A., Ohgami, R. S."A comprehensive analysis of RHOA mutation positive and negative angioimmunoblastic T-cell lymphomas by targeted deep sequencing, expression profiling and single cell digital image analysis". International Journal of Molecular Medicine 46, no. 4 (2020): 1466-1476. https://doi.org/10.3892/ijmm.2020.4686