Comprehensive Genomic Profiling of Adult T-Cell Lymphoblastic Lymphoma in Chinese Patients

Background:

T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor T cells that occurs mostly in adolescents and young adults. Extensive genomic analyses of T-LBL have discovered genes encoding adhesion molecules and extracellular matrix proteins in samples from T-LBL patients, with most studies being performed on patients in the Western hemisphere. We sought to define the mutational profile of T-LBL in Chinese patients.

Methods:

We collected 15 adult T-LBL biopsies from one center in China with confirmed pathologic diagnosis and treatment information. Median cohort age at diagnosis was 26.0 years. The male/female ratio was 13/2. DNA was extracted from formalin-fixed paraffin embedded samples, and targeted deep next generation sequencing (NGS) analyses were performed.

Results:

Mutation features were revealed in this Chinese T-LBL analysis. NOTCH1 mutations were found in 67% (10/15) of T-LBL patients (pts) with the highest mutation frequency. PHF6 mutations were seen in 53% (8/15) of cases. TP53mutations were seen in 53% (5/15) of T-LBL cases. JAK1 and JAK3 mutations were seen in 27% (4/15)of T-LBL cases respectively. Mutations at histone modification genesincluded SUZ12 (20%, 3/15), EZH2(13%, 2/15), and EP300 (7%,1/15). Other mutations included PTEN(27% 4/15), DNM2 (27% 4/15).

Discussion:

The aim of our study was to reveal the genomic landscape of Chinese T-LBL. The cohort collection was unbiased, the patients' features were in concordance with previous reports that the disease of T-LBL is mostly found in the young patients and shows male predominance. The most predominant somatic mutation wasNOTCH1, which is also usually seen in T-ALL. Mutations at histone modification genes were also seen in our study. NGS studies have identified epigenetic modifiers mutations as a hallmark of T-LBL, highlighting an attractive therapeutic target in this disease. In summary, this effort has identified novel mutation features in Chinese T-LBLs that can potentially lead to more effective treatments in Chinese population.