Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis
Open Access
- 1 February 2021
- journal article
- research article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 107 (2), 489-499
- https://doi.org/10.3324/haematol.2020.265991
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) are a group of complex clinicopathological entities that originate from TFH cells and share a similar mutation profile. Their diagnosis is often a challenge, particularly at an early stage, due to a lack of specific histological and immunophenotypic features, paucity of neoplastic T cells and prominent polymorphous infiltrate. We investigated whether the lymphoma associated RHOA Gly17Val (c.50G>T) mutation, occurring in 60% of cases, is present in the early ‘reactive’ lesions, and whether mutation analysis can help advance early lymphoma diagnosis. The RHOA mutation was detected by quantitative PCR with a locked nucleic acid (LNA) probe specific to the mutation, and a further PNA clamp oligonucleotide to suppress the amplification of the wild-type allele. The qPCR assay was highly sensitive and specific, detecting RHOA Gly17Val at an allele frequency of 0.03%, but not other changes in Gly17, nor in 61 controls. Among the 37 cases of AITL and PTCL-TFH investigated, RHOA Gly17Val was detected in 62.2% (23/37) of which 19 had multiple biopsies including preceding biopsies in 10 and follow up biopsies in 11 cases. RHOA Gly17Val was present in each of these preceding or follow up biopsies including 18 specimens that showed no evidence of lymphoma by combined histological, immunophenotypic and clonality analyses. The mutation was seen in biopsies 0-26.5 months (mean=7.87 months) prior to lymphoma diagnosis. Our results show that RHOA Gly17Val mutation analysis is valuable in the early detection of AITL and PTCL-TFH.Keywords
This publication has 32 references indexed in Scilit:
- Age-related mutations associated with clonal hematopoietic expansion and malignanciesNature Medicine, 2014
- Detection of the G17V RHOA Mutation in Angioimmunoblastic T-Cell Lymphoma and Related Lymphomas Using Quantitative Allele-Specific PCRPLOS ONE, 2014
- A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphomaNature Genetics, 2014
- Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomasNature Genetics, 2014
- Somatic RHOA mutation in angioimmunoblastic T cell lymphomaNature Genetics, 2014
- Peripheral T-cell Lymphomas of Follicular T-Helper Cell Derivation With Hodgkin/Reed-Sternberg Cells of B-cell LineageThe American Journal of Surgical Pathology, 2013
- Angioimmunoblastic T‐cell lymphoma with hyperplastic germinal centres (pattern 1) shows superior survival to patterns 2 and 3: a meta‐analysis of 56 casesHistopathology, 2012
- TET2andDNMT3AMutations in Human T-Cell LymphomaNew England Journal of Medicine, 2012
- TET2 Inactivation Results in Pleiotropic Hematopoietic Abnormalities in Mouse and Is a Recurrent Event during Human LymphomagenesisCancer Cell, 2011
- Angioimmunoblastic Lymphadenopathy with Dysproteinemia – Lack of a Prognostic Value of Clear Cell MorphologyOncology, 1997