title: Angioimmunoblastic T-cell Lymphomas With the RHOA p.Gly17Val Mutation Have Classic Clinical and Pathologic Features.
abstract: Angioimmunoblastic T-cell lymphoma (AITL) is a nodal-based mature T-cell lymphoma with distinctive clinical symptomatology and histology. Research into its pathogenesis supports a cellular derivation from follicular helper T cells and overexpression of genes related to B cells, follicular dendritic cells, and vascular growth. 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). We investigated a series of AITLs to compare RHOA mutated with wild-type case for clinicopathologic differences. Targeted exome and Sanger sequencing was performed on 27 AITLs and 10 PTCL-NOS. The RHOA G17V mutation was identified in 63% of the AITL cases and in none of the PTCL-NOS cases. The median variant allelic frequency was 14%, with a range of 0.4 to 50% in positive cases. RHOA G17V-mutated cases had a significantly higher incidence of splenomegaly and B symptoms at diagnosis, but there was no difference in overall survival between mutated and wild-type subgroups. Cases with the RHOA G17V mutation had a significantly higher mean microvessel density (P<0.01) and expressed a greater number of follicular helper T-cell markers (P<0.05) than wild-type cases. RHOA G17V is present in a significant proportion of angioimmunoblastic lymphomas and is associated with classic pathologic features of AITL. Additional studies are needed to provide a biological or functional link between altered RHOA function and these pathologic features.
authors.affiliation: *Department of Laboratory Medicine †Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH ‡Department of Pathology and Laboratory Medicine, UCLA Medical Center, Los Angeles, CA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Ondrejka
authors.forename: Bartosz
authors.initials: B
authors.lastname: Grzywacz
authors.forename: Juraj
authors.initials: J
authors.lastname: Bodo
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Chantana
authors.initials: C
authors.lastname: Polprasert
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Said
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Przychodzen
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D013163:Splenomegaly / Q000235:genetics / Q000473:pathology; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein