Comprehensive Genomic Profiling of Angioimmunoblastic T-Cell Lymphoma (AITL) in Chinese Patients

Background: Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, classified as a subtype of mature peripheral T-cell lymphoma. The 2016 revised WHO classification of lymphoid neoplasms proposed AITL as a nodal lymphoma derived from the T follicular helper cell. Extensive genomic analyses of AITL have discovered recurrent mutations in RHOA, TET2, DNMT3A, IDH2, and within genes of the T-cell receptor signaling pathway, with most studies being performed on patients in the Western hemisphere. We sought to define the mutational profile of AITL in Chinese patients. Methods: We collected 10 AITL biopsies from one center in China with confirmed pathologic diagnosis and treatment information. Diagnoses were independently confirmed by OrigiMed pathologists in all 10 AITL cases. Median cohort age at diagnosis was 61.1 years, and 60% (6/10) of the patients were older than 60 years. The male/female ratio was 8/2. In situ hybridization indicated Epstein-Barr virus positivity in 8/10 of AITL cases. DNA was extracted from formalin-fixed paraffin embedded samples, and targeted deep next generation sequencing (NGS) analyses were performed using the 450+ cancer genes panel. Results: Common and novel mutation features were revealed in this Chinese AITL analysis. As previously reported, TET2 mutations were found in 80% (8/10) of AITL patients (pts) with the highest mutation frequency, of which all the 8 pts harbored NMD/truncation and 6 pts harbored more than one mutation. RHOA mutations were seen in 60% (6/10) of cases, 4 cases were RHOA G17V while the other two were C16F and G17E/S26R, respectively. IDH2 R172 mutations were seen in 40% (4/10) of AITL cases. Co-occurring mutations of TET2 and RHOA were detected in the half of the cases (5/10), and 3 cases had concurrent TET2/RHOA/IDH2 mutations. DNMT3A mutations were seen in 30% (3/10) of AITLs cases, one case harbored two mutations including R882C. We also revealed novel mutation features. Recurrent mutations at histone modification genes included TIPARP (2 cases), KMT2C (2 cases), KMT2D (1 case). CRLF2 gene amplification was seen in a female patient. An intergenic PAX5 rearrangement was seen in 1 case along with MET and CFTR gene amplification. Tumor mutational burden (TMB) assessment indicated high TMB (>10 mutations/Mb) in the PAX5 rearrangement case while low TMB in the other nine cases. Discussion: The aim of our study was to reveal the genomic landscape of Chinese AITL. The cohort collection