Sequencing StudiesACCRF funded whole exome and whole genome sequencing projects at the Wellcome Trust Sanger Institute, MD Anderson, Memorial Sloan Kettering and Johns Hopkins. In addition, ACCRF facilitated an exon panel study by Foundation Medicine. An ACC bioinformatics consortium consolidated this information into cBioPortal (Multi-Institute Cohort of 1045 Adenoid Cystic Carcinoma patients) and published Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma (Ho et al., 2019).
ACCRF has supported the development of ACC PDX models to assist researchers in developing cell cultures, studying disease biology and screening drugs. Many of the PDX models were first published in a Laboratory Investigation article. They maintain the histology and gene expression patterns of the primary tumors from which they were derived.
Approximately 20 ACC PDX models are maintained at XenoSTART, a contract research organization providing an open drug screening platform under a contractual agreement with ACCRF. Academic and industry researchers may explore the efficacy and toxicity of their drugs in ACC preclinical models. ACCRF does not seek to obtain intellectual property from collaborators using the platform.
ACCRF has generated RNAseq data from many of the ACC PDX models and is developing a public tool to query the data. Interested researchers may inquire by email. In addition, RNA microarray expression data may be downloaded at:
Gene expression – Array Express (2012)
Gene expression – GEO (2012)
Gene expression – Array Express (2011)
Gene expression – GEO (2011)
Whole exome and whole genome sequencing was completed in 2015 on a subset of the ACC PDX models. The following file includes missense and nonsense mutations that were identified across 10 models:
The following table summarizes the genomic alterations found in these models:
Genomic Alterations in ACC PDX Models
| Model | MYB Fusion | MYB IHC | NOTCH Status | NOTCH IHC |
|---|---|---|---|---|
| ACCx2 | MYB-TGFBR3 | Positive | wild type | Low |
| ACCx5M1 | MYB-NFIB | Positive | Inactivated (S1004L) | Low |
| ACCx6 | MYB-TGFBR3 * | Positive | wild type | Low |
| ACCx9 | MYB-NFIB | Positive | Activated (I1680N) | High |
| ACCx11 | MYB-NFIB | Positive | Activated (3′ UTR duplication) | High |
| ACCx12 | MYB-RAD51B | Positive | wild type | Low |
| ACCx14 | MYB-NFIB | Positive | wild type | Low |
| ACCx16 | MYB-NFIB | Positive | wild type | Low |
| ACCx19 | MYB-NFIB | Positive | wild type | Low |
| ACCx22 | MYB-NFIB | Positive | wild type | Low |
Notes:
Whole genome sequencing was performed in 6 models: ACCx2, ACCx9, ACCx12, ACCx16, ACCx19 and ACCx22.
Whole exome sequencing was performed in 4 models: ACCx5M1, ACCx6, ACCx11 and ACCx14.
* Presumed given that ACCx2 (primary) and ACCx6 (lung mets) were derived from the same patient.
Several of these models are available for drug screening at START: ACCx2, ACCx5M1, ACCx6, ACCx9, ACCx11 and ACCx14.
Drug screening to determine efficacy and toxicity has been carried out extensively at START. Approximately 30 approved anticancer agents and 50 novel agents have been tested in tumor growth inhibition studies. Interested researchers may contact ACCRF to receive the publicly-available data.