RGD Reference Report - An Animal Model Further Uncovers the Role of Mutant BrafV600E during Papillary Thyroid Cancer Development. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

An Animal Model Further Uncovers the Role of Mutant BrafV600E during Papillary Thyroid Cancer Development.

Authors: Koelsch, Bernd  Theurer, Sarah  Staniszewska, Magdalena  Heupel, Jacqueline  Koch, Amelie  Mergener, Svenja  Walk, Franziska  Fischer, Christine  Kutritz, Andrea  Schmid, Kurt W  Kindler-Röhrborn, Andrea 
Citation: Koelsch B, etal., Am J Pathol. 2020 Mar;190(3):702-710. doi: 10.1016/j.ajpath.2019.11.006. Epub 2020 Jan 14.
RGD ID: 32716372
Pubmed: PMID:31953036   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ajpath.2019.11.006   (Journal Full-text)

Papillary thyroid carcinomas (PTCs) account for 90% of human thyroid cancer cases, which represent 1% of all cancer cases. They are likely to develop from papillary thyroid microcarcinomas (PTMCs), found in up to 36% of healthy individuals, due to rare progression events (0.01%). Although the prognosis of PTCs is excellent, 5% to 10% of tumors display an unfavorable outcome. About 45% of PTCs exhibit activating BRAFV600E mutations. Rats of the inbred BD strains postnatally exposed to the carcinogen N-ethyl-N-nitrosourea developed PTMCs, which closely resembled their human counterparts judging from their histology, size, and marginal tendency to progress. DNA sequencing revealed mutations in exon 15 of the Braf gene identical to the human BRAFV600E mutation in 82% of the cases. Predominantly a 50:50 ratio of wild-type to mutant Braf alleles was seen regardless of tumor size or animal age, indicating that the Braf mutation is an early, if not the initial, event in rat PTMC development. Surprisingly, most PTMCs carrying a confirmed BrafV600E mutation did not display BrafV600E protein expression. As the BrafV600Egene is supposed to be the driver in PTC development, down-regulation of expression should contribute to the low risk for progression of PTMC. This model system will enable further insights into the molecular mechanisms of PTMC initiation and progression to PTC, further translating into targeted tumor prevention strategies/therapies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
thyroid gland papillary carcinoma  ISOBraf (Rattus norvegicus)32716372; 32716372DNA:missense mutation:cds and p.V600E(rat)RGD 
thyroid gland papillary carcinoma  IMP 32716372DNA:missense mutation:cds and p.V600E(rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Braf  (B-Raf proto-oncogene, serine/threonine kinase)

Genes (Mus musculus)
Braf  (Braf transforming gene)

Genes (Homo sapiens)
BRAF  (B-Raf proto-oncogene, serine/threonine kinase)


Additional Information