The discovery of the recurrent t(6;9) translocation in ACC that often results in the MYB-NFIB fusion oncogene has opened up the possibility of developing transgenic models of ACC. Two genetically engineered mouse models (GEMMs) have been published.

DNA helix
MYB-NFIB/MMTV-CRE/Ink4a +/-/Arf+/-EMM (Jiang et al., Oral Oncology, 2019)

Mice engineered to express the MYB-NFIB transgene (MYB exons 1-14 fused to NFIB exon12) under control of Cre-activated MMTV promoter show upregulated transgene expression (by RT-PCR) in salivary and breast tissues and develop B-cell neoplasms, but not salivary tumors, potentially stemming from lack of MYB protein expression observed in the salivary gland. Crossing of MYB-NFIB/MMTV-CRE and Ink4a+/-/Arf+/-mice (modeling the lack of p16 that is observed in some ACCs) led to the formation of a large breast tumor with ACC-like histology that expresses high levels of MYB protein. A cell line (UFBT) retains high levels of MYB expression and is sensitive to MYB inhibition.

MYB-NFIB/MMTV-CRE/p53fl/fl GEMM (Mikse et al., Oncotarget, 2016)

Mice engineered to express the MYB-NFIB transgene (MYB exons 1-14 fused to NFIB exon 8) under control of the Cre-activated MMTV promoter did not show high levels of MYB protein expression in the salivary gland (even upon direct injection of adenovirus-Cre directly) and failed to form tumors of any kind. Crossing of MYB-NFIB/MMTV-CRE mice with the p53fl/fl mouse model led to the formation of poorly differentiated breast adenocarcinomas in mice with heterozygous loss of p53 and lymphoma in mice with homozygous loss of p53. Breast tumors forming in the MYB-NFIB/MMTV-CRE/p53fl/+ mice showed elevated levels of MYB and keratin protein but lacked classical ACC histology. Ubiquitous overexpression of MYB-NFIB under control of the UCRE promoter led to high levels of MYB staining in the salivary gland, breast, and other organs, and ultimately caused death due to kidney abnormalities, with breast hyperplasia observed in female animals.

ACCRF is supporting additional GEMM efforts to address the role that wild type/full length MYB plays in ACC tumor initiation and whether activated NOTCH1 accelerates MYB-driven ACC tumorigenesis. At the moment, these models are in development and are not available.