Integrative genomic analysis focused on cell cycle genes for MYC-driven aggressive mature B-cell lymphoma

Abstract

MYC is a transcriptional factor that regulates growth and proliferation through cell cycle pathways. MYC alterations, in particular MYC rearrangements, are important in assessing the prognosis of aggressive B-cell lymphoma. In this study, we focused on the impact of nine major cell cycle genes for MYC-driven aggressive mature B-cell lymphoma and analyzed the mutational status using targeted next generation sequencing. Our 40 cases of aggressive mature B-cell lymphomas included 5 Burkitt lymphomas, 17 high-grade B-cell lymphomas and 18 diffuse large B-cell lymphomas with MYC breaks in 100%, 88% and 11%, respectively. Our data allowed a molecular classification into four categories partially independent from the histopathological diagnosis but correlating with the Ki-67 labelling index: (I) harboring TP53 and CDKN2A mutations, being highly proliferative, (II) with MYC rearrangement associated with MYC and/or ID3 mutations, being highly proliferative, (III) with MYC rearrangement combined with additional molecular changes, being highly proliferative, and (IV) with a diverse pattern of molecular alterations, being less proliferative. Taken together, we found that mutations of TP53 , CDKN2A , MYC and ID3 are associated with highly proliferative B-cell lymphomas that could profit from novel therapeutic strategies.

MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and <i>TP53</i>/p53 – a Nordic Lymphoma Group study

“…The MYC high TP53/p53 + subgroup of patients had unfavorable clinical characteristics, with most having highly proliferative tumors, with non-classic morphology and being in a high-risk MIPI group. The presence of tumors with both aberrations had been noted in other studies, 23,26,39,40 but this is the first time that an association with prognostic and clinicopathological parameters in MCL is reported. The negative effect of MYC overexpression combined with TP53 mutations, excluding patients with wild-type TP53 but high levels of p53 protein, was also confirmed.…”

Transcriptomic analysis of spleen B cell revealed the molecular basis of bursopentin on B cell differentiation

“…Additionally, the Myc family is reported to regulate B cell growth and proliferation [ 47 ], which is related to the activated BCR signaling the differentiation of B cells [ 48 , 49 ]. The ZBTB family is reported to be involved in the development, differentiation, and function of B cells [ 50 ].…”