RHOA G17V mutation in angioimmunoblastic T-cell lymphoma: A potential biomarker for cytological assessment

Pei Hang Lee, Shao Wen Weng, Ting Ting Liu, Huey Ling You, Chun Kai Liao, Ming Chung Wang, Wan Ting Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations

Abstract

Background: The World Health Organization, in a 2016 revision, introduced recurrent genetic abnormalities for classifying mature T- and NK-cell neoplasms. However, the role of genetic analyses from lymph node aspiration cytology is still not elucidated. We hypothesize that the use of genetic analyses may increase the accuracy of diagnosis from cytological preparations. Methods: Fifty-seven formalin-fixed paraffin-embedded (FFPE) samples were collected for next-generation sequencing (NGS) targeting potential driver mutations including TET2, DMN3TA, IDH2, RHOA, STAT3, and STAT5B. Competitive allele-specific TaqMan polymerase chain reaction (cast-PCR) was performed to validate the mutation status by using FFPE and preoperative fine needle aspiration cytology (FNAC) samples. Results: Among these six candidate genes, only IDH2 and RHOA mutations were significantly more frequent in nodal subtypes, angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) (P = .002 and <0.001, respectively). All genes exhibited different mutation patterns except RHOA with a hotspot mutation involving the Gly17 residue. The RHOA G17V mutation was found in 15 (75%) of 20 AITL and two (22%) of nine PTCL, NOS. Cast-PCR using FFPE samples showed 100% concordance with NGS. Among 12 lymph node aspirates, the preliminary diagnoses were suspicious for lymphoma (3, 25%), atypical lymphoid cells (3, 25%) and benign/negative (6, 50%). Cast-PCR detected the RHOA G17V mutation in six (75%) of eight RHOA-mutated aspirates and revealed negative results in all (100%) of four wild-type aspirates, with an 83.3% (10/12) concordance comparing to FFPE samples. Conclusions: The RHOA G17V mutation serves as a useful biomarker for cytological assessment in AITL. The use of cast-PCR is valuable in the diagnosis of malignant lymphomas from cytological preparations, and thus avoiding the potential risks of invasive procedures.

Original languageEnglish
Article number104294
JournalExperimental and Molecular Pathology
Volume110
DOIs
StatePublished - 10 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Angioimmunoblastic T-cell lymphoma
  • Fine-needle aspiration cytology
  • Peripheral T-cell lymphoma
  • RHOA

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