The basic building blocks of research are widely available for researchers of common cancers. However, a concerted effort must be undertaken to develop, maintain and distribute tumor specimens, cell lines and mouse models for rare cancers.
The Salivary Gland Tumor Biorepository (SGTB) collects, maintains and distributes biospecimens and cell lines, and provides qualified researchers with materials for basic and translational research on salivary gland tumors. The SGTB is centralized at M.D. Anderson and includes Johns Hopkins, New York University, Rhode Island Hospital, the University of California at San Francisco, the University of Mississippi, the University of Pittsburgh and the University of Virginia as consortium members with expertise in salivary gland tumors.
The SGTB website provides access to an inventory of available specimens as well as application instructions for any interested researcher globally. The SGTB operates under a contract with the National Institute of Dental and Craniofacial Research (NIDCR). ACCRF Executive Director Jeff Kaufman serves on the Tissue Utilization Committee.
Two ACC cell lines were immortalized with the human papillomavirus (HPV) as described in this International Journal of Cancer article. ACC-52 and ACC-112 were created by Dr. Lurdes Queimado. The cells grow slowly and require careful handling.
At the moment, no other cell lines are widely considered to be valid ACC models. A few years ago, there were several cell lines purported to be derived from ACC patients. However, ACCRF and its affiliated investigators came to realize through STR analysis that the available cell lines were cross-contaminated and misidentified. ACCRF sounded an early warning that was later confirmed in this PLoS ONE article.
Batches of ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2 were all found to be misidentified. Theoretically, there may be batches that have not been cross-contaminated, but they have not been made available to ACCRF-affiliated researchers nor have the primary tumor samples from which they were derived. One cell line, SACC-83, was found to be genotypically distinct but, given the issues experienced with the other cell lines, would require further validation before being considered a valid ACC model.
ACCRF is supporting several attempts to develop new ACC cell lines that are not immortalized with HPV. They will be made available to the research community once they are validated by multiple investigators and quality controls ensure that the problems of the past won’t recur.
Patient-Derived Xenografts (PDX)
ACCRF has supported Dr. Christopher Moskaluk at the University of Virginia in his attempts to create patient-derived xenograft models of ACC. The effort has been successful with the development of 17 models as described in this Laboratory Investigations article. In all cases, the histologic appearance and gene expression patterns of the originating tumor were recapitulated in the subsequent xenograft, and 11 of 12 xenografts analyzed had MYB locus rearrangements.
The PDX models have been valuable in providing plentiful fresh and frozen tissue for genomic and phosphoproteomic studies as well as attempts to develop cell lines. They have also been instrumental for preclinical drug screening in support of clinical trial concepts.
The PDX models have been extensively characterized with much of the data available online at the Adenoid Cystic Carcinoma Database. An update of the drug screening data is available in this spreadsheet file.
Transgenic Mouse Models
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 a transgenic model of ACC. ACCRF is supporting such efforts at the Dana-Farber Cancer Institute and the University of Virginia, while NIDCR is supporting another effort at M.D. Anderson. Complementary approaches are being tried with different promoters (MMTV and PSP), variants of the MYB-NFIB fusion and systems for inducing its over-expression.
At the moment, these models are in development and are not available.