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BIOMARKER:

BRAF V600E + TERT mutation

i
Other names: TERT, Telomerase Reverse Transcriptase, Telomerase-Associated Protein 2, Telomerase Catalytic Subunit, HEST2, EST2, TCS1, TP2, TRT, PFBMFT1, DKCA2, DKCB4, CMM9, HTR, BRAF, B-raf proto-oncogene, B-raf proto-oncogene, Serine/threonine kinase, V-Raf murine sarcoma viral oncogene homolog B, Serine/threonine-protein kinase B-Raf, Proto-oncogene B-Raf, BRAF1, RAFB1, B-raf proto-oncogene Serine/threonine-protein kinase, Murine sarcoma viral (V-Raf) oncogene homolog B1, B-raf serine/threonine-protein, 9
Entrez ID:
3ms
Genetic Trio of BRAF and TERT Mutations and rs2853669TT in Papillary Thyroid Cancer Aggressiveness. (PubMed, J Natl Cancer Inst)
SNP rs2853669T>C dramatically refines the prognostic power of BRAF V600E and TERT promoter mutations to a higher precision, suggesting the need for including this SNP in the current genetic-based risk prognostication of PTC.
Journal
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BRAF (B-raf proto-oncogene) • TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • BRAF mutation • BRAF V600 • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation • TERT mutation + BRAF V600E
6ms
LENVATINIB IN COMBINATION WITH ONCOPROTEIN TARGETED MAPK INHIBITORS IN DIFFERENTIATED AND DEDIFFERENTIATED THYROID CANCERS (ATA 2023)
Mice with dedifferentiated tumors treated with 4 weeks of either lenvatinib or dabrafenib/trametinib (dab/tram) for Braf/Arid1a or tipifarnib for Hras/p53 demonstrated tumor progression or stability (% change tumor volume: Braf/Arid1a: vehicle +238. Combination MAPK signaling blockade and angiogenesis inhibition leads to profound anti‐tumor responses across the spectrum of thyroid cancers in GEMMs.
Late-breaking abstract • Combination therapy
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BRAF (B-raf proto-oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
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BRAF V600E • BRAF V600 • NRAS G12 • BRAF V600E + TERT mutation • CD31 expression • HRAS G12V
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Mekinist (trametinib) • Tafinlar (dabrafenib) • Lenvima (lenvatinib) • Zarnestra (tipifarnib)
6ms
A Prospective, Multicenter Study of Molecular-Based Initial Thyroidectomy for Bethesda V/VI Cytology (ATA 2023)
Based on immediate post‐operative ATA risk stratification by histology, appropriate initial TL and TT occurred for all patients with MT low‐ and high‐risk alterations. However, MT intermediate‐risk results (typically BRAF‐like) were associated with histologies in all 3 ATA risk categories. The patients are being followed to monitor for tumor recurrence while additional clinical factors will be explored in order to continue refining optimal initial extent of surgery.
Clinical • Cytology
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53)
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BRAF V600E • BRAF V600 • BRAF V600E + TERT mutation
8ms
Telomerase upregulation induces progression of mouse BrafV600E-driven thyroid cancers and triggers non-telomeric effects. (PubMed, Mol Cancer Res)
These models constitute useful pre-clinical tools to understand the cell-autonomous and microenvironment-related consequences of Tert-mediated progression in advanced thyroid cancers and other aggressive tumors carrying TPMs. Implications: Telomerase-driven cancer progression activates pathways that can be dissected and perhaps therapeutically exploited.
Preclinical • Journal
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TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • BRAF V600 • BRAF V600K • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation • TERT overexpression
9ms
TERT Promoter Mutations, But Not BRAFV600EMutation, Correlate With The American Thyroid Association And TNM Staging Systems And Predict Outcome Of Differentiated Thyroid Cancer (ENDO 2023)
TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems. The combination of high-risk ATA or TNM stage IV with TERT promoter mutations is highly predictive of development of PD predicting PD in 100% of cases with these combinations.
Late-breaking abstract
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TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation • TERT mutation + BRAF V600E
11ms
IMPACT OF THE BRAF V600E GENE MUTATION IN PATIENTS WITH PAPILLARY THYROID CANCER FROM NORTHERN ECUADORIAN ANDES (ENDO 2023)
Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*
Clinical
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600E + TERT mutation
1year
PD-L1 Expression in Anaplastic Thyroid Carcinoma: A Transcontinental Study of 151 Cases (USCAP 2023)
In this large-scale study evaluating PD-L1 expression in ATC specimens, most of the ATCs were PD-L1-positive, which provides a rationale for immunotherapy in this aggressive malignancy. The positivity rate was lower in small biopsy specimens, having implications for clinical decision-making and formulation of management guidelines. PD-L1 expression did not correlate with BRAF V600E or TERT promoter mutation status.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TERT (Telomerase Reverse Transcriptase)
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PD-L1 expression • BRAF V600E • BRAF V600 • PD-L1 negative • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation • BRAF V600E + PD-L1 expression
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PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
1year
Aggressive Trabecular Histology in Papillary Thyroid Carcinoma: Intra- and Inter-observer Reproducibility in Visual Identification and Association with BRAFV600e, TP53, TERT Promoter Mutations and Total Mutation Burden (USCAP 2023)
Trabecular pattern identification by visual assessment shows a moderate degree of inter-observer reproducibility. The patten is significantly associated with BRAF V600e mutations suggesting aggressive behavior potentially derives from consequences of this specific mutation.
Tumor mutational burden
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • TERT (Telomerase Reverse Transcriptase)
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TP53 mutation • BRAF V600E • BRAF V600 • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation
over1year
QUANTITATIVE MOLECULAR ASSAY ASSISTS IN A DEFINITIVE CANCER DIAGNOSIS AMONG PATIENTS WITH THYROID NODULES (ATA 2022)
Sensitive molecular assays have been established to specifically detect and quantify VAFs of BRAF V600E and TERT promoter variants using the dPCR approach. Quantitative molecular assays may facilitate definitive malignancy diagnoses among patients with thyroid nodules harboring such variants, and a high VAF of each variant alone or their coexistence at various VAFs increases the association with unfavourable clinico‐pathological features of the tumor.
Clinical
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600 • BRAF V600E + TERT mutation
almost2years
Tert mutant promoter mouse model induces cancer progression of BrafV600E-driven thyroid tumors (EACR 2022)
Braf+Tert animals partially responded to MAPK pathway inhibition (dabrafenib plus trametinib), showing that this crucial pathway remains relevant in these specimens. These pointed to key cancer functional processes that might inform new routes for therapeutic intervention in telomerase-mediated aggressive thyroid cancers. Conclusion These cancer models of telomerase reactivation provide excellent pre-clinical settings to understand the regulatory mechanisms and biological underpinnings of TPM-induced progression of thyroid (and other tumors) to aggressive disease, and to explore novel therapeutic strategies.
Preclinical
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BRAF (B-raf proto-oncogene) • TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • BRAF V600 • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation
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Mekinist (trametinib) • Tafinlar (dabrafenib)
2years
Tert mutant promoter mouse model induces cancer progression in BrafV600E-driven thyroid tumors: A novel tool to understand the biology of telomerase-reactivated cancers (AACR 2022)
Braf+Tert animals partially responded to MAPK pathway inhibition (dabrafenib plus trametinib), showing that MAPK signaling remains relevant in these specimens. Interestingly, RNA sequencing of Tert-reactivated murine thyroid tumors showed unique transcriptomic profiles (compared to BrafV600E alone), suggesting that downstream effects, other than the canonical Tert-mediated telomere maintenance, operate in cancers harboring TPMs. These cancer models of telomerase reactivation provide excellent pre-clinical settings to understand the regulatory mechanisms and biological underpinnings of TPM-induced progression of thyroid and other tumors, and to explore novel therapeutic strategies.
Preclinical
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BRAF (B-raf proto-oncogene) • TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • BRAF V600 • BRAF V600K • TERT mutation • BRAF V600E + TERT mutation • TERT promoter mutation
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Mekinist (trametinib) • Tafinlar (dabrafenib)
over2years
[VIRTUAL] Association of Bethesda category and molecular mutation in patients undergoing thyroidectomy (AHNS 2021)
BRAFV600E, TERT and RET mutations were associated with aggressive thyroid cancers. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with different Bethesda categories and to tailor patient treatment.
Clinical
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RET (Ret Proto-Oncogene) • TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • NRAS mutation • BRAF V600 • RET mutation • TERT mutation • BRAF V600E + TERT mutation
over2years
[VIRTUAL] Droplet digital polymerase chain reaction testing of RAS, BRAF and TERT for pre-operative molecular testing of thyroid nodules (AHNS 2021)
Combining cytology with ddPCR analysis of TERT, BRAF and RAS mutations can improve the diagnostic accuracy of thyroid FNABs.
Polymerase Chain Reaction
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BRAF (B-raf proto-oncogene) • TERT (Telomerase Reverse Transcriptase)
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BRAF V600E • BRAF V600 • HRAS mutation • NRAS Q61 • NRAS Q61R • NRAS G12 • TERT mutation • BRAF V600E + TERT mutation • NRAS Q61K + BRAF V600E • TERT promoter mutation • HRAS G12V • NRAS G12V