Journal article
G-protein coupled receptor expression patterns delineate medulloblastoma subgroups
Acta neuropathologica communications, Vol.1(1), pp.66-66
2013
DOI: 10.1186/2051-5960-1-66
PMCID: PMC3893540
PMID: 24252460
Abstract
Background: Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy.
Results: Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset.
Conclusions: Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors.
Details
- Title: Subtitle
- G-protein coupled receptor expression patterns delineate medulloblastoma subgroups
- Creators
- Kelsey L Whittier - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 2524 JCP, USAErin A Boese - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 2524 JCP, USAKatherine N Gibson-Corley - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USAPatricia A Kirby - Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, USABenjamin W Darbro - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 2524 JCP, USAQining Qian - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 2524 JCP, USAWendy J Ingram - Queensland Children’s Tumour Bank, Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaThomas Robertson - Pathology Queensland, Royal Children’s Hospital, Brisbane, QLD, AustraliaMarc Remke - Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaMichael D Taylor - Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaM Sue O’Dorisio - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 2524 JCP, USA
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica communications, Vol.1(1), pp.66-66
- Publisher
- BioMed Central
- DOI
- 10.1186/2051-5960-1-66
- PMID
- 24252460
- PMCID
- PMC3893540
- ISSN
- 2051-5960
- eISSN
- 2051-5960
- Language
- English
- Date published
- 2013
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984093366702771
Metrics
16 Record Views