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Patterns of Tumor Infiltrating Lymphocytes in Adenoid Cystic Carcinoma of the Head and Neck
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Development and Characterization of MYB-NFIB Fusion Expression in Adenoid Cystic Carcinoma

1
Department of Otolaryngology, Head and Neck Surgery, University of California-San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94080, USA
2
School of Medicine, University of California-San Francisco, San Francisco, CA 94080, USA
3
Graduate Group in Biostatistics, Center for Computational Biology, University of California-Berkeley, Berkeley, CA 94720, USA
4
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Scott A. Ness
Cancers 2022, 14(9), 2263; https://doi.org/10.3390/cancers14092263
Received: 5 April 2022 / Revised: 21 April 2022 / Accepted: 24 April 2022 / Published: 30 April 2022
(This article belongs to the Special Issue Salivary Gland Adenoid Cystic Carcinoma)
Chromosomal t(6;9) translocation is commonly found in adenoid cystic carcinoma (ACC) of the salivary gland. This genetic rearrangement results in the fusion of MYB and NFIB genes. Despite the frequent occurrence of t(6;9) translocation and MYB-NFIB gene fusion, the nature of chimeric MYB-NFIB proteins and their potential relevance in the development and behavior of ACC remains poorly understood. The lack of validated ACC cell lines, harboring the t(6;9) translocation with defined MYB-NFIB fusion protein, has restricted fusion-specific functional studies. Hence, we sought to characterize and establish in vitro and in vivo models of a MYB-NFIB fusion protein expressing system in ACC. Defining the nature and functional aspect of MYB-NFIB fusion proteins may not only improve our understanding of the disease but also contribute to the identification of molecular targets that are druggable and can be developed for future therapeutic purpose.
Adenoid cystic carcinoma (ACC) is the second most common cancer type arising from the salivary gland. The frequent occurrence of chromosome t(6;9) translocation leading to the fusion of MYB and NFIB transcription factor genes is considered a genetic hallmark of ACC. This inter-chromosomal rearrangement may encode multiple variants of functional MYB-NFIB fusion in ACC. However, the lack of an ACC model that harbors the t(6;9) translocation has limited studies on defining the potential function and implication of chimeric MYB-NFIB protein in ACC. This report aims to establish a MYB-NFIB fusion protein expressing system in ACC cells for in vitro and in vivo studies. RNA-seq data from MYB-NFIB translocation positive ACC patients’ tumors and MYB-NFIB fusion transcript in ACC patient-derived xenografts (ACCX) was analyzed to identify MYB breakpoints and their frequency of occurrence. Based on the MYB breakpoint identified, variants of MYB-NFIB fusion expression system were developed in a MYB-NFIB deficient ACC cell lines. Analysis confirmed MYB-NFIB fusion protein expression in ACC cells and ACCXs. Furthermore, recombinant MYB-NFIB fusion displayed sustained protein stability and impacted transcriptional activities of interferon-associated genes set as compared to a wild type MYB. In vivo tumor formation analysis indicated the capacity of MYB-NFIB fusion cells to grow as implanted tumors, although there were no fusion-mediated growth advantages. This expression system may be useful not only in studies to determine the functional aspects of MYB-NFIB fusion but also in evaluating effective drug response in vitro and in vivo settings. View Full-Text
Keywords: adenoid cystic carcinoma; chromosomal t(6; 9) translocation; MYB; MYB-NFIB fusion adenoid cystic carcinoma; chromosomal t(6; 9) translocation; MYB; MYB-NFIB fusion
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MDPI and ACS Style

Humtsoe, J.O.; Kim, H.-S.; Jones, L.; Cevallos, J.; Boileau, P.; Kuo, F.; Morris, L.G.T.; Ha, P. Development and Characterization of MYB-NFIB Fusion Expression in Adenoid Cystic Carcinoma. Cancers 2022, 14, 2263. https://doi.org/10.3390/cancers14092263

AMA Style

Humtsoe JO, Kim H-S, Jones L, Cevallos J, Boileau P, Kuo F, Morris LGT, Ha P. Development and Characterization of MYB-NFIB Fusion Expression in Adenoid Cystic Carcinoma. Cancers. 2022; 14(9):2263. https://doi.org/10.3390/cancers14092263

Chicago/Turabian Style

Humtsoe, Joseph O., Hyun-Su Kim, Leilani Jones, James Cevallos, Philippe Boileau, Fengshen Kuo, Luc G.T. Morris, and Patrick Ha. 2022. "Development and Characterization of MYB-NFIB Fusion Expression in Adenoid Cystic Carcinoma" Cancers 14, no. 9: 2263. https://doi.org/10.3390/cancers14092263

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