RGD Reference Report - Association of LRP1B Mutation With Tumor Mutation Burden and Outcomes in Melanoma and Non-small Cell Lung Cancer Patients Treated With Immune Check-Point Blockades. - 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

Association of LRP1B Mutation With Tumor Mutation Burden and Outcomes in Melanoma and Non-small Cell Lung Cancer Patients Treated With Immune Check-Point Blockades.

Authors: Chen, Hao  Chong, Wei  Wu, Qian  Yao, Yueliang  Mao, Min  Wang, Xin 
Citation: Chen H, etal., Front Immunol. 2019 May 21;10:1113. doi: 10.3389/fimmu.2019.01113. eCollection 2019.
RGD ID: 150429775
Pubmed: PMID:31164891   (View Abstract at PubMed)
PMCID: PMC6536574   (View Article at PubMed Central)
DOI: DOI:10.3389/fimmu.2019.01113   (Journal Full-text)

Background: Tumor mutation burden (TMB) have been served as the most prevalent biomarkers to predict immunotherapy response. LRP1B (low-density lipoprotein receptor-related protein 1B) is frequently mutated in melanoma, non-small cell lung cancer (NSCLC) and other tumors; however, its association with TMB and survival in patients with immunotherapy remains unknown. Methods: We curated somatic mutation data and clinicopathologic information from 332 melanoma immunotherapy samples for discovery and 113 NSCLC samples for further corroboration. Bayesian variants non-negative matrix factorization was used to extract tumor mutational signatures. Multivariate Cox and logistic regression models were applied to adjust confounding factors. The CIBERSORT and GSEA algorithm were separately used to infer leukocyte relative abundance and significantly enriched pathways. Results: Patients with LRP1B mutation were identified to be associated with prolonged survival in both immunotherapy cohort. Higher tumor mutation burden was found in LRP1B mutated patients, and the association remained significant after controlling for age, gender, stage, mutations in TP53 and ATR, and mutational signatures. Immune response and cell cycle regulation circuits were among the top enriched pathways in samples with LRP1B mutations. Conclusion: Our studies suggested sequencing even a single, frequently mutated gene may provide insight into genome-wide mutational burden, and may serve as a biomarker to predict immune response.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung non-small cell carcinoma amelioratesIAGP 150429775DNA:mutations:multiple: (human)RGD 
lung non-small cell carcinoma amelioratesISOLRP1B (Homo sapiens)150429775; 150429775DNA:mutations:multiple: (human)RGD 
melanoma amelioratesIAGP 150429775DNA:mutations:multiple: (human)RGD 
melanoma amelioratesISOLRP1B (Homo sapiens)150429775; 150429775DNA:mutations:multiple: (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Melanoma amelioratesIAGP 150429775DNA:mutations:multiple: RGD 
Non-small cell lung carcinoma amelioratesIAGP 150429775DNA:mutations:multiple: RGD 
Objects Annotated

Genes (Rattus norvegicus)
Lrp1b  (LDL receptor related protein 1B)

Genes (Mus musculus)
Lrp1b  (low density lipoprotein-related protein 1B)

Genes (Homo sapiens)
LRP1B  (LDL receptor related protein 1B)


Additional Information