^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

RB1 wild-type

i
Other names: RB1, RB Transcriptional Corepressor 1, Protein Phosphatase 1 Regulatory Subunit 130, Prepro-Retinoblastoma-Associated Protein, Retinoblastoma-Associated Protein, Retinoblastoma 1, P110-RB1, P105-Rb, Pp110, PRb, Exon 17 Tumor GOS561 Substitution Mutation Causes Premature Stop, GOS563 Exon 17 Substitution Mutation Causes Premature Stop, Retinoblastoma Suspectibility Protein, Osteosarcoma, PPP1R130, OSRC, RB, Rb, pRb
Entrez ID:
Related biomarkers:
2ms
Differentiating MYCN-amplified RB1 wild-type retinoblastoma from biallelic RB1 mutant retinoblastoma using MR-based radiomics: a retrospective multicenter case-control study. (PubMed, Sci Rep)
SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCNampRB1+/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCNampRB1+/+ and RB1-/- retinoblastoma subtypes.
Retrospective data • Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • RB1 mutation • RB1 wild-type
10ms
CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
Tumor mutational burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
|
FoundationOne® Heme CDx
10ms
CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
Tumor mutational burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
|
FoundationOne® Heme CDx
10ms
Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype. (PubMed, J Neurooncol)
Patients with glioblastoma IDH-wildtype harboring 4q12 amplification rarely have restricting DWI patterns compared to their wildtype counterparts, in which this DWI pattern is present in ~ 50% of patients. This suggests that some phenotypic imaging characteristics can be identified among molecular subtypes of IDH-wildtype glioblastoma.
Journal
|
RB1 (RB Transcriptional Corepressor 1)
|
RB1 mutation • IDH wild-type • RB1 wild-type
1year
Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B. (PubMed, Cell Rep Med)
Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).
Journal • Liquid biopsy • Biopsy
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1)
|
MET amplification • RB1 wild-type
|
Tepmetko (tepotinib)
1year
Tumor-derived biomarkers predict efficacy of B7H3 antibody-drug conjugate treatment in metastatic prostate cancer models. (PubMed, J Clin Invest)
Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies.
Preclinical • Journal • Metastases
|
TP53 (Tumor protein P53) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • CD276 (CD276 Molecule) • SLFN11 (Schlafen Family Member 11)
|
TP53 mutation • TP53 wild-type • AR positive • SLFN11 expression • CD276 expression • RB1 wild-type
1year
Alterations in EGFR and PDGFRA are associated with the localization of contrast-enhancing lesions in glioblastoma. (PubMed, Neurooncol Adv)
And PDGFRA alteration correlated with multiple lesions. Our results suggest that clarifying the association between driver genes and tumor localization may be useful in clinical practice, including prognosis prediction.
Journal
|
EGFR (Epidermal growth factor receptor) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
|
IDH wild-type • RB1 wild-type
over1year
A Study of Abemaciclib in Recurrent Glioblastoma (clinicaltrials.gov)
P2; Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2024
Trial completion date • Trial primary completion date
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK6 (Cyclin-dependent kinase 6)
|
CDKN2A deletion • CDK4 amplification • IDH wild-type • RB1 wild-type
|
OncoPanel™ Assay
|
Verzenio (abemaciclib)
over1year
Integrative analysis of a large real-world cohort of small cell lung cancer identifies distinct genetic subtypes and insights into histological transformation. (PubMed, Cancer Discov)
Finally, profiling cases of SCLC containing oncogenic drivers typically associated with NSCLC demonstrates that SCLC transformation may occur across multiple distinct molecular cohorts of NSCLC. These novel and unsuspected genetic features of SCLC may help personalize treatment approaches for this fatal form of cancer.
Journal • Real-world evidence • Real-world
|
TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
|
TP53 mutation • STK11 mutation • CCNE1 amplification • RB1 wild-type
over1year
MRI Features for Identifying MYCN-amplified RB1 Wild-type Retinoblastoma. (PubMed, Radiology)
© RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue
Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • RB1 wild-type
almost2years
Comprehensive analysis of 3,600 small cell lung cancer cases reveals rare genetic subtypes and multiple mechanisms of histological transformation (AACR 2023)
Our work underscores the existence of genetic subtypes in SCLC, including rare subtypes with potential clinical utility. Findings from this study provide an improved understanding of genetic subtypes in SCLC and better inform mechanisms of transformation to SCLC from NSCLC, that may further guide the development of personalized therapies for subsets of patients with this fatal tumor.
Clinical
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • KDR (Kinase insert domain receptor)
|
TP53 mutation • EGFR mutation • NTRK1 fusion • ALK fusion • CCNE1 amplification • RB1 wild-type
almost2years
Enrollment closed
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK6 (Cyclin-dependent kinase 6)
|
CDKN2A deletion • CDK4 amplification • IDH wild-type • RB1 wild-type
|
OncoPanel™ Assay
|
Verzenio (abemaciclib)
over2years
Immune Checkpoint Blockade Outcome in Small-Cell Lung Cancer and Its Relationship With Retinoblastoma Mutation Status and Function. (PubMed, JCO Precis Oncol)
SCLC patients with RB1 WT status or lower RB1 LOF signature scores by transcriptomics have better outcomes with ICB monotherapy.
Retrospective data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker
|
STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)
|
STK11 mutation • KEAP1 mutation • RB1 mutation • RB1 wild-type
|
Opdivo (nivolumab) • Yervoy (ipilimumab)
over2years
Rb tumor suppressor in small cell lung cancer: Combined genomic and immunohistochemical analysis with a description of a distinct Rb-proficient subset. (PubMed, Clin Cancer Res)
This is the largest study to-date to concurrently analyze Rb by NGS and immunohistochemistry in SCLC, identifying a 6% rate of Rb proficiency. Pathologic-genomic data implicate NSCLC-related progenitors as a putative source of Rb-proficient SCLC. Consistent upstream Rb inactivation via CDKN2A/p16↓ and CCND1/cyclinD1↑ suggests potential utility of CDK4/6 inhibitors in this aggressive SCLC subset. The study also clarifies technical aspects of Rb status determination in clinical practice, highlighting the limitations of exon-only sequencing for RB1 interrogation.
Journal
|
FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • CCND1 (Cyclin D1)
|
STK11 mutation • KEAP1 mutation • CDKN2A mutation • RB1 mutation • CCND1 amplification • CCND1 expression • CCND1-H • RB1 wild-type
over2years
A Study of Abemaciclib in Recurrent Glioblastoma (clinicaltrials.gov)
P2; Trial primary completion date: Jun 2022 --> Jun 2023
Trial primary completion date
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK6 (Cyclin-dependent kinase 6)
|
CDKN2A deletion • CDK4 amplification • IDH wild-type • RB1 wild-type
|
FoundationOne® CDx • OncoPanel™ Assay
|
Verzenio (abemaciclib)
over2years
Clinical response to tepotinib according to circulating tumor (ct) DNA biomarkers in patients with advanced NSCLC with high-level MET amplification (METamp) detected by liquid biopsy (LBx). (ASCO 2022)
Tepotinib showed meaningful activity, especially in first line, in the first trial of a MET inhibitor in EGFR WT NSCLC with high-level METamp to enroll based on a convenient LBx assay. BL biomarker analyses indicated focal METamp, MYC/RB1 WT, and low ctDNA MAF were associated with improved outcomes. Serial LBx could monitor molecular response and evaluate resistance.
Clinical • Liquid biopsy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1)
|
MET amplification • EGFR wild-type • MET exon 14 mutation • RB1 mutation • RB1 wild-type
|
Guardant360® CDx
|
Tepmetko (tepotinib)
almost3years
Early proliferative response via [18]FLT-PET/CT and serum TK1 activity are predictive biomarkers for synergistic effect of sequential cell cycle targeted therapy in sarcoma (AACR 2022)
CDK4/6 inhibitor, abemaciclib, was used to reactivate the Rb pathway followed by treatment with gemcitabine or WEE1-kinase-inhibitor, to target the enriched S and G2/M phase cells post-abemaciclib removal. Our study presents an innovative treatment strategy inhibiting the Rb pathway followed by S or G2/M pathway sequentially resulting in synergistic cell killing in those cells/tumors with wild-type Rb. We also incorporate real-time PET imaging and serum TK1 as non-invasive indicators of response to the treatment strategy. The study with PDX models also identified biomarkers of cell proliferation to be used in conjunction with PET imaging to provide the pre-clinical rationale to translate our findings into clinical trials for this aggressive disease.
CCND1 (Cyclin D1)
|
CCND1 overexpression • RB1 wild-type
|
gemcitabine • Verzenio (abemaciclib)
almost3years
HPV51-associated Leiomyosarcoma: A Novel Class of TP53/RB1-Wildtype Tumor With Predilection for the Female Lower Reproductive Tract. (PubMed, Am J Surg Pathol)
Overall, in our pan-LMS analysis, HPV reads were identified in a subset of TP53/RB1-wildtype LMS. For all HPV51-associated LMS, the striking absence of any detectable TP53 or RB1 mutations and predilection for the female lower reproductive tract supports our hypothesis that high-risk HPV can be an alternative tumorigenic mechanism in this distinct class of LMS.
Journal
|
TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • TSC1 (TSC complex subunit 1)
|
TP53 mutation • RB1 mutation • RB1 wild-type
|
FoundationOne® Heme CDx
3years
Enrollment change • Trial withdrawal
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CASP3 (Caspase 3)
|
CDKN2A deletion • RB1 wild-type
|
FoundationOne® CDx
|
Keytruda (pembrolizumab) • Verzenio (abemaciclib)
over3years
Abemaciclib + Pembrolizumab In Glioblastoma (clinicaltrials.gov)
P2; Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
Trial completion date • Trial primary completion date
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CASP3 (Caspase 3)
|
CDKN2A deletion • RB1 wild-type
|
FoundationOne® CDx
|
Keytruda (pembrolizumab) • Verzenio (abemaciclib)
almost4years
Abemaciclib + Pembrolizumab In Glioblastoma (clinicaltrials.gov)
P2; Trial completion date: Aug 2022 --> Dec 2022 | Trial primary completion date: Aug 2022 --> Dec 2022
Trial completion date • Trial primary completion date
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CASP3 (Caspase 3)
|
CDKN2A deletion • RB1 wild-type
|
FoundationOne® CDx
|
Keytruda (pembrolizumab) • Verzenio (abemaciclib)