830MO - Integrated driver mutations profile of Chinese NK/T cell lymphoma

Background

Natural killer (NK)/T-cell lymphoma (NKTCL) is a rare type of non-Hodgkin’s lymphoma prevalent in East Asian countries. There is still a significant lack of effective therapeutic targets for the treatment of NKTCL. In this study, we investigated the driver mutation profile of 15 Chinese patients with NKTCL to determine its possible mechanisms of formation and identify therapeutic targets.

Methods

We performed whole-exome sequencing (WES) on paired tumor/normal samples from 15 Chinese patients diagnosed with NKTCL. We performed a K-Means prediction based on the mutation profiles of proto-oncogenes retrieved from the NCG database. The NKTCL mutation patterns were analyzed using the Bayesian non-negative matrix factorization (Bayesian-NMF) method.

Results

Among the 15 Chinese NKTCL patients, the primary site of the lymphomas was the colon (40%), followed by ileum (26.7%), and small intestine (26.7%), while one patient’s was the rectum. Furthermore, the mean tumor mutation burden (TMB) was 1.04 (0.29-2.55). The RETSAT gene showed the highest mutation frequency (26.7%), followed by SNRNP70 (20%), and ADGRL3 (13.3%). Among the oncogenes, the genes with the six highest gene mutation frequencies included ARID1B, ERBB3, KMT2D, POT1, TET2, and TP53 (13.3%). NMF analysis of 509 single-nucleotide variants (SNVs) from 15 NK T-cell lymphoma samples identified three mutational signatures; signature one (46.69% SNV) and signature three (32.09% SNV) were well known C > T transition at CpG sites. Similar to feature 22 in the COSMIC database, the second feature (21.23% SNV) was dominated by the T > A transition. Furthermore, most samples featured signatures one and three as their main mutation patterns.

Conclusions

In this study, the genome-wide analysis of 15 Chinese NK/T-cell lymphoma patients revealed that RETSAT, and SNRNP70 were the genes with the highest mutation frequencies. In addition, NK/T-cell lymphoma patients showed higher mutation frequencies in ARID1B, and ERBB3 oncogenes. These findings suggested the presence of possible driver genes, along with therapeutic targets for NKTCL. Furthermore, they illustrate characteristic mutation patterns, which are valuable for guiding future NKTCL research.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.