TY - JOUR
T1 - Angioimmunoblastic T-cell lymphomas with the RHOA p.Gly17Val mutation have classic clinical and pathologic features
AU - Ondrejka, Sarah L.
AU - Grzywacz, Bartosz
AU - Bodo, Juraj
AU - Makishima, Hideki
AU - Polprasert, Chantana
AU - Said, Jonathan W.
AU - Przychodzen, Bartlomiej
AU - Maciejewski, Jaroslaw P.
AU - Hsi, Eric D.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Angioimmunoblastic T-cell lymphoma
KW - RHOA G17V
KW - T-cell non-Hodgkin lymphoma
UR - http://www.scopus.com/inward/record.url?scp=84959156656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959156656&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000000555
DO - 10.1097/PAS.0000000000000555
M3 - Article
C2 - 26574844
AN - SCOPUS:84959156656
SN - 0147-5185
VL - 40
SP - 335
EP - 341
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 3
ER -