RGD Reference Report - RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR. - 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

RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR.

Authors: Sakre, Nneha  Wildey, Gary  Behtaj, Mohadese  Kresak, Adam  Yang, Michael  Fu, Pingfu  Dowlati, Afshin 
Citation: Sakre N, etal., Oncotarget. 2017 Jan 24;8(4):5992-6002. doi: 10.18632/oncotarget.13362.
RGD ID: 152995517
Pubmed: PMID:27863413   (View Abstract at PubMed)
PMCID: PMC5351607   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.13362   (Journal Full-text)

Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all lung cancers. Currently there are no targeted therapies to treat SCLC. Our genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR amplification. Here, we examine the translational potential of this observation. RICTOR was the most frequently amplified gene observed (~14% patients), and co-amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells. In parallel, cells with RICTOR copy number (CN) gain showed increased sensitivity to three mTOR inhibitors, AZD8055, AZD2014 and INK128 in cell growth assays, with AZD2014 demonstrating the best inhibition of downstream signaling. SCLC cells with RICTOR CN gain also migrated more rapidly in chemotaxis and scratch wound assays and were again more sensitive to mTOR inhibitors. The overall survival in SCLC patients with RICTOR amplification was significantly decreased (p = 0.021). Taken together, our results suggest that SCLC patients with RICTOR amplification may constitute a clinically important subgroup because of their potential response to mTORC1/2 inhibitors.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RICTORHumanlung small cell carcinoma severityIAGP DNA:CNV and amplification:exon (human)RGD 
RictorRatlung small cell carcinoma severityISORICTOR (Homo sapiens)DNA:CNV and amplification:exon (human)RGD 
RictorMouselung small cell carcinoma severityISORICTOR (Homo sapiens)DNA:CNV and amplification:exon (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rictor  (RPTOR independent companion of MTOR, complex 2)

Genes (Mus musculus)
Rictor  (RPTOR independent companion of MTOR, complex 2)

Genes (Homo sapiens)
RICTOR  (RPTOR independent companion of MTOR complex 2)


Additional Information