{"entity":{"id":"rhoa-g17v","kind":"biomarker","name":"RHOA G17V","aka":["RHOA G17V","RHOA Gly17Val","RHOA mutation","T-follicular-helper lymphoma mutation"],"tldr":"A single change in a small signalling protein, found in about two thirds of one kind of T-cell lymphoma. It is useful because it is specific to the tumour cells, while the other mutations in the same disease are also present in normal blood cells.","summary":"RHOA is a small GTPase. The G17V substitution produces a protein that does not bind GTP and that also blocks the function of the normal copy, so it acts against the wild-type protein rather than simply being inactive.\n\nIt was reported in 68% of angioimmunoblastic T-cell lymphoma samples, and remarkably every case carrying it also carried a TET2 mutation; the RHOA mutation was found only in the tumour cells, while TET2 mutations were found in tumour and non-tumour haematopoietic cells alike, which places the TET2 lesion earlier, in the stem cell (Sakata-Yanagimoto 2014). An independent series found it in 22 of 35 angioimmunoblastic cases, 67%, and in 8 of 44 cases of peripheral T-cell lymphoma not otherwise specified, 18%, alongside recurrent TET2, DNMT3A and IDH2 mutations and less frequent FYN, ATM, B2M and CD58 lesions (Palomero 2014).\n\nThe ordering matters clinically as well as biologically: this is a lymphoma that grows out of clonal haematopoiesis, which is part of why it occurs in older people and why hypomethylating agents have activity in it.","asOf":"2026-09-30","links":[{"label":"Sakata-Yanagimoto et al., Nat Genet 2014: somatic RHOA G17V in angioimmunoblastic T-cell lymphoma","url":"https://doi.org/10.1038/ng.2872"},{"label":"Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma","url":"https://doi.org/10.1038/ng.2873"}],"tags":["biomarker","lymphoma"],"related":[],"cancers":["angioimmunoblastic-t-cell-lymphoma","peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["cgp"],"targets":["rhoa","tet2","dnmt3a","fyn"],"drugs":["azacitidine","romidepsin"],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","clonal-haematopoiesis"],"terms":["ngs","driver-mutation","clonal-evolution-theory"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"rhoa","measurement":"sequencing-variant","scoringRule":{"text":"Targeted sequencing of RHOA codon 17 on tissue, reported as mutated or wild-type, usually within a T-cell lymphoma panel alongside TET2, DNMT3A and IDH2. Sensitivity matters because the tumour cells are often a minority of an angioimmunoblastic node, which is full of reactive B cells, plasma cells and vessels.","quote":"Here we report somatic RHOA mutations encoding a p.Gly17Val alteration in 68% of AITL samples.","source":"https://doi.org/10.1038/ng.2872","sourceLabel":"Sakata-Yanagimoto et al., Nature Genetics 2014"},"thresholds":[],"definedBy":{"label":"Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma","url":"https://doi.org/10.1038/ng.2873"},"tests":[],"assays":[],"companionDiagnostics":[],"forPatient":"This result supports the diagnosis when the biopsy is difficult to read, which it often is in this lymphoma. It does not yet select a licensed drug, although the related mutations in the same disease are the reason hypomethylating treatments are used and studied in it."},"route":"/biomarkers/rhoa-g17v/","neighbours":{"cancer":[{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"}],"target":[{"id":"dnmt3a","kind":"target","name":"DNA methyltransferase 3A (DNMT3A)","route":"/targets/dnmt3a/"},{"id":"fyn","kind":"target","name":"FYN","route":"/targets/fyn/"},{"id":"rhoa","kind":"target","name":"RHOA","route":"/targets/rhoa/"},{"id":"tet2","kind":"target","name":"TET2","route":"/targets/tet2/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"romidepsin","kind":"drug","name":"Romidepsin","route":"/drugs/romidepsin/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"}],"term":[{"id":"clonal-evolution-theory","kind":"term","name":"Clonal evolution and the ecological view of cancer","route":"/terms/clonal-evolution-theory/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}]}}