Recently, a novel recurring somatic mutation in RHOA, encoding p.Gly17Val, was discovered in nearly 70% of AITLs and in a smaller proportion of peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS).
These analyses identified highly recurrent epigenetic factor mutations in TET2, DNMT3A and IDH2 as well as a new highly prevalent RHOA mutation encoding a p.Gly17Val alteration present in 22 of 35 (67%) angioimmunoblastic T cell lymphoma (AITL) samples and in 8 of 44 (18%) PTCL, not otherwise specified (PTCL-NOS) samples.
For example, genetic alterations have been discovered, including signal transducer and activator of transcription (STAT)3 and STAT5b mutations in several PTCLs, disease-specific ras homolog family member A (RHOA) mutations in angioimmunoblastic T cell lymphoma (AITL), and recurrent translocations at the dual specificity phosphatase 22 (DUSP22) locus in anaplastic lymphoma receptor tyrosine kinase (ALK)-negative anaplastic large cell lymphomas (ALCLs).
We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five T<sub>FH</sub> antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL (<i>TET2</i>, <i>DNMT3A, IDH2, RHOA</i> and <i>PLCG1</i>) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features.
This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.
While our case suggests that circulating D-2HG is not a reliable marker of IDH mutation in AITL, more cases need to be studied to arrive at a definite conclusion.
Genome wide sequencing studies have dissected the repertoire of the genetic alterations driving AITL uncovering a highly recurrent Gly17Val somatic mutation in the small GTPase RHOA and major role for mutations in epigenetic regulators, such as TET2, DNMT3A and IDH2, and signaling factors (e.g., FYN and CD28).
Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%).
However, in angioimmunoblastic lymphadenopathy (AILD), first described as a nonneoplastic proliferation associated with immunodeficiency, the heterogeneity of TCR and IgH gene rearrangements suggest that some cases may harbor multiple lymphoid clones.
We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five T<sub>FH</sub> antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL (<i>TET2</i>, <i>DNMT3A, IDH2, RHOA</i> and <i>PLCG1</i>) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features.
Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%).
Among these, CCR4 expression and the CD21(+) network in RHOA-mutated AITL cases were more extensive than in the RHOA mutation-negative AITL cases (P<0.05).
MRI-derived measures of liver and spleen stiffness as well as laboratory-based APRI and FIB-4 scores are highly associated with imaging findings of portal hypertension in children and young adults with AILD and thus might be useful for predicting portal hypertension impending onset and directing personalized patient management.
Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%).
Genome wide sequencing studies have dissected the repertoire of the genetic alterations driving AITL uncovering a highly recurrent Gly17Val somatic mutation in the small GTPase RHOA and major role for mutations in epigenetic regulators, such as TET2, DNMT3A and IDH2, and signaling factors (e.g., FYN and CD28).
The frequencies of TET2/DNMT3A and SRSF2 variants could support the hypothesis that TET2/DNMT3A mutations occurred in an early progenitor cell, which later progressed to both the AITL and CMML clones.