Case Report: Multiple Chromosomal Translocations Including Novel CIITA-CREBBP Fusion and Mutations in a Follicular Lymphoma

Abstract

The pathogenesis of follicular lymphoma is a multi-step process, in which chromosomal translocation between immunoglobulin heavy chain (IgH) and anti-apoptotic B-cell lymphoma 2 (BCL2), namely IgH-BCL2, is an earliest step, followed by other genetic/genomic alterations including but not limited to mutation of CREB binding protein (CREBBP). MHC class II transactivator (CIITA) is a transcription regulator responsible for expression of MHC class II molecules including HLA-DR in human. We report herein a novel fusion gene involving CIITA and CREBBP in a patient with a low-grade follicular lymphoma (FL) but with high Ki-67 proliferation index. In addition, our patient also harbors CREBBP mutation. Together, we postulate that total loss of CREBBP function may contribute, in part, to the lymphoma genesis. Furthermore, this patient has addition rare (TBL1XR1-TP63) and common (IgH-BCL2) chromosomal translocations and multiple mutations including BCL2, BRAF, MUTYH, and STAT6.

The Pathologic and Genetic Characteristics of Extranodal NK/T-Cell Lymphoma

“…Major histocompatibility complex (MHC) class II transactivator (CIITA) is the master regulator of MHC class II gene expression [137]. The mutation of CIITA was reported in 12 of 123 (10%) ENKTLs and is also frequently found in other types of malignant lymphoma, including primary mediastinal large B-cell lymphoma, follicular lymphoma, and Burkitt lymphoma [138][139][140]. The genomic aberrations of CIITA in B-cell lymphoma frequently comprise structural genomic rearrangements and missense, nonsense, and frameshift mutations, leading to a decreased expression of MHC-II genes and promoting the immune escape of the tumor [138].…”

IKZF1::CIITA, a novel fusion transcript in a case of relapsed B‐cell acute lymphoblastic leukemia

“…19 Fusion of CREBBP with CIITA has been reported in follicular lymphoma; however, in that case, CIITA did not lose its function as the initial 19 exons of CIITA were retained in the fusion transcript. 20 Antigen-presenting cells present tumor cells bound with MHC class II to T-helper cells, thus resulting in apoptosis of the tumor cells. 21 In our case, disrupted CIITA function and the resultant reduced MHC-II-mediated tumor cell death may be a contributing factor for the disease relapse.…”