The ACCRF Research Agenda has led to the generation of enormous data sets spanning a wide array of platforms. The foundation’s intent is to make these data sets easily accessible online to all interested researchers. Although such a web portal may take some time to develop, there are some current resources available.
ACCRF 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. The lists of somatic mutations from four published studies’ appendices are included in this file of published mutations. Two of the studies include lists of chromosomal rearrangements derived from whole genome sequencing.
The general conclusion of these studies is that ACC tumors have relatively quiet genomes with few somatic mutations and only one highly recurrent genomic alteration, a rearrangement of the MYB gene on chromosome 6. Small clusters of mutations are evident in the NOTCH, FGF, IGF and PI3K pathways, and a broad group of chromatin remodeling factors also are altered in many cases.
An ACC bioinformatics consortium is consolidating information on published genomic alterations in ACC as well as unpublished alterations from several institutions. This data set eventually will be available through cBioPortal (currently showing the Memorial Sloan Kettering study results).
Expression and CGH Array Studies
The Wellcome Trust Sanger Institute sequencing study referenced above included parallel gene expression and comparative genomic hybridization (CGH) arrays:
A study from the University of Florida and MD Anderson identified a unifying gene expression signature for ACC. The expression data is available at:
A study from the University of Gothenburg and MD Anderson correlated copy number alterations with clinical parameters. The CGH data is available at:
Patient-Derived Xenograft (PDX) Models
ACCRF has supported the development of ACC PDX models to assist researchers in developing cell lines, studying the disease biology and screening drugs. Most of the models, now numbering more than 20, have been created at the University of Virginia, although a few additional models are available from other institutions. Approximately 12 of the ACC PDX models are maintained at South Texas Accelerated Research Therapeutics (START), a contract research organization providing an open drug screening platform under a contractual agreement with ACCRF. Academic and industry researchers may expolore the efficacy and toxicity of their drugs in ACC preclinical models. ACCRF does not seek to obtain intellectual property from collaborators using the platform.
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.
The Adenoid Cystic Carcinoma Database is a website created by the University of Virginia with ACCRF support. The website contains descriptive details and histological images as well as aCGH, gene expression, phosphoproteomics and drug screening data. The RNA expression data may be downloaded in CEL files. Alternatively, similar data is available at:
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
(recurrent and intergenic)
Mutations in selected genes
(missense/nonsense and coding)
ACCx2 MYB-TGFBR3, CHD18-TRIO BRD2, CREBBP, PCDH8 ACCx5M1 MYB-NFIB MAML2, MUC16, NOTCH1, RASSF1, SMARCAL1 ACCx6 MYB-TGFBR3 * BRD2, CREBBP, FGFRL1, PCDH8 ACCx9 MYB-NFIB, VPS13B-PARK2 KIT, NOTCH1, RB1 ACCx11 MYB-NFIB CDH3, CREBBP ACCx12 MYB-RAD51B, EYS-RASA1 BRD2, CDH1, CDH2, CREBBP, PCDH15, PCDHGB7 ACCx14 MYB-NFIB CDH18, FBXW7, KDM6A ACCx16 MYB-NFIB, NFIB-LINC00326, TAF13-SEPT12 ARID1B, CDH12, PCDHB10 ACCx19 MYB-NFIB, NFIB-TRPM3, TAF13-NDRG3, CDH18-FLRT2 ARID1B, BRCA2, CCNB1, ERBB3, KDM6A, PCDH7 ACCx22 MYB-NFIB, EYS-SMARCA2 ATM, CDH13, CREBBP, FGF13
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.