Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma with a poor prognosis: the 5-year survival rate is approximately 30%. Somatic driver mutations have been found in TET2, IDH2, DNMT3A, RHOA, FYN, PLCG1, and CD28, whereas germline susceptibility to AITL has to our knowledge not been studied. The homogenous Finnish population is well suited for studies on genetic predisposition. Here, we performed an exome-wide rare variant analysis in 23 AITL patients. No germline mutations were found in the driver genes, implying that they are not frequently involved in genetic AITL predisposition. Potentially pathogenic variants present in at least two patients and showing significant (p < 0.01) enrichment in our sample set were found in ten genes: POLK, PRKCB, ZNF676, PRRC2B, PCDHGB6, GNL3L, TTC36, OTOG, OSGEPL1, and RASSF9. The most significantly enriched variants, causing p.Lys469Ter in a splice variant of POLK and p.Pro588His in PRKCB, are intriguing candidates as Polk deficient mice display a spontaneous mutator phenotype, whereas PRKCB was recently shown to be somatically mutated in 33% of another peripheral T-cell lymphoma, adult T-cell lymphoma. If validated, our findings would provide new insight into the pathogenesis of AITL, as well as tools for early detection in susceptible individuals.

Tumor Microenvironment CD8 T and Treg Cells–related Genes Signature Distinguishes Distinct Prognosis and Targeted Therapies Response in Endometrial Cancer

“…OTOG has been hardly studied in tumors. Mutated OTOG has a role in angioimmunoblastic T-cell lymphoma lymphomagenesis 64. In our research, E2F1, OTOG, and TTK were all highly expressed in EC and correlated with a worse prognosis and poor pathological factors.…”

“…Mutated OTOG has a role in angioimmunoblastic T-cell lymphoma lymphomagenesis. 64 In our research, E2F1, OTOG, and TTK were all highly expressed in EC and correlated with a worse prognosis and poor pathological factors. High methylation of PPP1R16B existed in colon cancer and glioblastoma.…”

RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis

“…RASSF9 is a member of RAS-association domain family. There is growing evidence that the dysregulation of RASSF9 expression is closely associated with many human diseases, including cancer [ 7 , 24 – 26 ]. RASSF9 was initially identified as a protein based on interaction with the cytoplasmic domain of PAM (peptide acylglycine α-amino monooxygenase) through a yeast two-hybrid screen [ 27 ].…”

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma

“…The patients may have abnormal laboratory test results such as increased eosinophil, increased polyclonal immunoglobulin, increased lactate dehydrogenase, positive anti-human globulin test, and increased rheumatoid factor titer [7][8][9]. AITL has a poor prognosis and the 5-year median survival rate was only 32% [10][11][12]. The complete or partial disappearance of lymph node structure and significant enlargement of the subcortical area were common in AITL.…”