Abstract
BackgroundTumor mutation burden is an emerging biomarker for immunotherapy. Although several clinical trials for immunotherapy in lymphoma have been carried out, the mutation burden of various lymphomas is not well known yet. Thus, the objective of this study was to compare tumor mutation burden of various non-Hodgkin lymphomas using panel based massively parallel sequencing.MethodsWe conducted 405 gene panel based massively parallel sequencing of 300 non-Hodgkin lymphomas and investigate the number of SNV/Indel in each lymphoma.ResultsThe number of SNV/Indel was higher in mature B-cell lymphoma than in mature T- and NK-cell lymphoma. (P < 0.001) The number of SNV/Indel in primary mediastinal large B-cell lymphoma and primary diffuse large B-cell lymphoma of the central nervous system was the highest, which was significantly higher than that in diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS).(P = 0.030 and P = 0.008, respectively) The SNV/Indel number in EBV-positive DLBCL NOS was significantly lower than that in DLBCL NOS. (P = 0.048) Peripheral T-cell lymphoma, NOS showed no significant difference in the number of SNV/Indel from extranodal NK/T-cell lymphoma, nasal type (P = 0.942) or angioimmunoblastic T-cell lymphoma (P = 0.739). The number of SNV/Indel in anaplastic large cell lymphoma, ALK-positive was significantly lower than that in anaplastic large cell lymphoma, ALK-negative (P = 0.049). It was the lowest among all the lymphomas considered.ConclusionVarious lymphomas have different mutation burdens. Thus, tumor mutation burden can be used as a promising biomarker for immunotherapy in lymphomas.
Highlights
Tumor mutation burden is an emerging biomarker for immunotherapy
The gene panel of LymphomaSCAN was constructed by adding genes known to be associated with hematologic malignancies to a common gene panel shared with other XSCANs for discussions between oncologists and hematopathologists
primary mediastinal large B-cell lymphoma (PMLBL) is a distinct subtype of EBV-positive diffuse large B-cell lymphoma (DLBCL) variants and is known to have a gene expression profile that overlaps with the profile of classic Hodgkin lymphoma [39, 40]
Summary
Tumor mutation burden is an emerging biomarker for immunotherapy. several clinical trials for immunotherapy in lymphoma have been carried out, the mutation burden of various lymphomas is not well known yet. Tumor mutation burden (TMB) is one of the most valuable biomarkers for identifying patients who are likely to respond to immune checkpoint blockade [1,2,3,4]. If the neoplasm progresses, mutations are likely to accumulate This is due to the instability of DNA, and due to tumor evolution for evading immune surveillance and for cancer survival [17,18,19]. In this respect, comparing the number of mutations of different tumors and within the same tumor group can provide interesting information about these malignancies
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