News - RB1 mutation + TP53 mutation

Prognostic and predictive significance of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas and their utility as an adjunct to accurate diagnosis-An eight-year retrospective study. (PubMed, Indian J Gastroenterol)

G3NETs are genetically different from NECs. Use of immunohistochemistry for p53 in addition to histomorphology may facilitate accurate categorization of NEC and G3NET. Mutated p53 may also be used as an independent prognostic marker in neuroendocrine tumors of GIT and pancreas.

1 month ago

Retrospective data • Journal

RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)

TP53 mutation • RB1 mutation • TP53 expression • RB1 mutation + TP53 mutation

2ms

Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma. (PubMed, JTO Clin Res Rep)

SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

2 months ago

Journal • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)

TP53 mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • RB1 mutation • EGFR L858R + EGFR exon 21 deletion • RB1 mutation + TP53 mutation

9ms

Folliculin (FLCN) Alterations in Thyroid Carcinoma: Incidence, Significance and Extraordinary Role as a Driver Gene in an Aggressive Mixed Papillary and Oncocytic Thyroid Carcinoma (USCAP 2024)

FLCN alterations are exceedingly rare in TCa with an incidence of pathogenic changes below 1%. However, FLCN may exceptionally serve as a key driver mutation in TCa, based on our index patient. Identification of FLCN mutations may be clinically important due to possible presence of a germline mutation predisposing to renal tumors and potential responsiveness to immune checkpoint inhibitors.

9 months ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1) • FLCN (Folliculin) • PAX8 (Paired box 8)

TP53 mutation • TMB-L • RB1 mutation • TTF1 expression + PD-L1 expression • FLCN mutation • NKX2-1 expression • RB1 mutation + TP53 mutation • TTF1 expression

MSK-IMPACT

11ms

Comprehensive Analysis of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and Associated mRNA Risk Signature in Hepatocellular Carcinoma. (PubMed, Anal Cell Pathol (Amst))

In addition, this study constructed a protein interaction network network including METTLs and mRNA risk signature genes related to tumor microenvironment remodeling based on single-cell sequencing. In conclusion, this study provides a theoretical basis for the mechanism, biomarker screening, and treatment of HCC.

11 months ago

Journal • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • METTL1 (Methyltransferase 1, TRNA Methylguanosine) • METTL3 (Methyltransferase Like 3)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

1year

A novel orthotopic murine model of neuroendocrine bladder cancer: insights into the molecular drivers of small cell bladder cancer (SCBC) (SUO 2023)

We developed a novel genetically engineered orthotopic murine model of SCBC which is histologically and morphologically similar to human SCBC. Gene expression profiling of neuroendocrine bladder tumors from these mice suggest FOXA2 may play a role in the initiation and development of the neuroendocrine phenotype. Ongoing work seeks to further characterize the role of FOXA2 in neuroendocrine differentiation and identify other genetic and epigenetic markers that may cooperatively contribute to the development of this aggressive variant of bladder cancer.

1 year ago

Preclinical

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • FOXA2 (Forkhead Box A2) • SYP (Synaptophysin)

TP53 mutation • MYC expression • TP53 expression • RB1 mutation + TP53 mutation

1year

POU2F3: A Sensitive and Specific Diagnostic Marker for Neuroendocrine-low/negative Small Cell Lung Cancer. (PubMed, Am J Surg Pathol)

One case of esophageal NE tumor was nuclear-positive, while the normal proliferating squamous epithelium was strongly membrane-stained. This is the largest cohort of clinical samples to confirm that POU2F3 is a highly sensitive and specific diagnostic marker for NE-low/negative SCLC.

1 year ago

Journal

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NKX2-1 (NK2 Homeobox 1) • POU2F3 (POU Class 2 Homeobox 3)

TP53 mutation • RB1 mutation • POU2F3 expression • RB1 mutation + TP53 mutation

1year

IMMUNOCOMPETENT MODELING OF PLEOMORPHIC LIPOSARCOMA (CTOS 2023)

A genetically engineered RPP mice reliably produced soft-tissue tumors consistent with pleomorphic liposarcoma, which immunological findings consist with other soft-tissue sarcomas. This model may demonstrate utility in testing treatments for this rare disease, including immunomodulatory therapies.

1 year ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M)

TP53 mutation • PTEN mutation • RB1 mutation • RB1 mutation + TP53 mutation

over1year

Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era. (PubMed, Clin Transl Oncol)

EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations.

over 1 year ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)

TP53 mutation • EGFR mutation • RB1 mutation + TP53 mutation

over1year

Mutational-Copy Number Variation Profile and Immunotherapy Drivers in Neuroendocrine Lung Carcinomas: PD-L1, Microsatellite Instability, DNA Mismatch Repair Genes Expression and Tumor Mutational Burden in a Series of 30 Cases (AMP Europe 2023)

In this series of lung neuroendocrine carcinomas, TP53 and RB1 mutations were the most prevalent. No tumors showed H-MSI or dMMR. Only 3 expressed PD-L1.

over 1 year ago

Clinical • Mismatch repair • Tumor mutational burden • Microsatellite instability • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • NKX2-1 (NK2 Homeobox 1) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • SYP (Synaptophysin) • HNF1A (HNF1 Homeobox A)

PD-L1 expression • TP53 mutation • MSI-H/dMMR • PTEN mutation • ARID1A mutation • STK11 mutation • RB1 mutation • MYCL amplification • RB1 mutation + TP53 mutation

Oncomine Tumor Mutation Load Assay

over1year

Epithelial-mesenchymal transition-related gene prognostic index and phenotyping clusters for hepatocellular carcinoma patients. (PubMed, Cancer Genet)

Half-maximal inhibitory concentration (IC50) revealed that cluster C2 patients were more sensitive to chemotherapeutic and antiangiogenic agents. These findings may guide risk stratification and precision therapy for HCC patients.

over 1 year ago

Journal • IO biomarker

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • TGFB1 (Transforming Growth Factor Beta 1)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

over1year

Multiparametric characterization of early-stage SCLC human tumors reveals novel patient subgroups based on specific molecular to immune landscape associations (AACR 2023)

Here we show a gene signature that can subclassify early-stage SCLC patients according to their clinical, molecular and immune features, and provides prognostic value independently of the NAPI classification. Since immunogenicity of the tumor impacts response to immunotherapy, we speculate that this gene signature might predict therapy response and therefore contribute to tailored treatment of SCLC.

over 1 year ago

Clinical • IO biomarker

TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • RB1 (RB Transcriptional Corepressor 1) • CD8 (cluster of differentiation 8) • TOP2A (DNA topoisomerase 2-alpha) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule) • CD79A (CD79a Molecule) • CD3D (CD3d Molecule) • TWIST1 (Twist Family BHLH Transcription Factor 1) • CD2 (CD2 Molecule) • MS4A1 (Membrane Spanning 4-Domains A1) • XIRP2 (Xin Actin Binding Repeat Containing 2) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1)

TP53 mutation • RB1 mutation • IDO1 expression • RB1 mutation + TP53 mutation

over1year

Patient-derived cell-based pharmacogenomic platform to uncover resistance mechanisms and novel therapeutics for advanced lung cancer (AACR 2023)

Among EGFR-TKI treatment groups, Osimertinib resistant group was enriched in EMT-like subtype 2 with vanishing EGFR T790M mutation and activating TGF-β pathway...Our PDC pharmacogenetic platform predict plausible drug candidates and markers for refractory lung cancer patients. We expect further studies for precision medicine by novel analysis and cohort expansion.

over 1 year ago

Clinical • Metastases

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • TGFB1 (Transforming Growth Factor Beta 1)

TP53 mutation • EGFR mutation • EGFR T790M • RB1 mutation • MYC expression • RB1 mutation + TP53 mutation

Tagrisso (osimertinib)

over1year

Clinical and transcriptomic analysis demonstrates improved survival and unique gene expression signatures among SCLC arising in patients with minimal tobacco use (AACR 2023)

These data demonstrate that SCLC arising from patients with minimal smoking histories confers a more favorable prognosis and harbors unique RNA signatures with potential therapeutic implications. We anticipate these results will shift the current clinical practice toward routine evaluation of non-RB1 or TP53-mediated drivers of oncogenesis among low pack-year patients with SCLC and promote further work in identifying novel therapies for this population.

over 1 year ago

Clinical • BRCA Biomarker • Omic analysis

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • MUTYH (MutY homolog) • POU2F3 (POU Class 2 Homeobox 3) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)

TP53 mutation • PALB2 mutation • RB1 mutation • MLH1 mutation • RB1 mutation + TP53 mutation

over1year

SKP2 knockout induces macrophage infiltration in p53/Rb1 null transgenic mouse models of osteosarcoma and drives gene expression correlated with improved survival in patients (AACR 2023)

Taken together, our new findings indicate that SKP2 modulation in OS may induce a vigorous anti-tumor immune activation especially in the form of macrophage and lymphocyte infiltration into the tumor microenvironment.

over 1 year ago

Preclinical

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • SKP2 (S-phase kinase-associated protein 2)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

almost2years

Clinical impact of mutations in driver oncogenes and TP53/RB1 in advanced prostate cancer. (ASCO-GU 2023)

In a cohort of aggressive PCa, oncogenic driver mutations were associated with significant differences in prognosis. ETS fusions and SPOP mutations correlated with improved outcomes for men with localized disease at presentation. TP53 loss was associated with worse prognosis, as was the combination with RB1 loss, across the disease spectrum.

almost 2 years ago

Clinical • Metastases

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • CDK12 (Cyclin dependent kinase 12) • SPOP (Speckle Type BTB/POZ Protein) • FOXA1 (Forkhead Box A1)

TP53 mutation • CDK12 mutation • RB1 mutation • SPOP mutation • RB1 mutation + TP53 mutation

almost2years

Histopathologic and Molecular Features of Lung Non-neuroendocrine Carcinomas with Co-inactivation Mutations of TP53 and RB1 Genes (USCAP 2023)

O ur study demonstrate s that the co-inactivation of TP53 and RB1 mutation s is identified in a small proportion of no n- NEC of t he lu ng . Interestingly, lung adenocarcinomas with co-inactivation of TP53 and RB1 seem to have a higher mutation rate in EGFR and a lower rate of KRAS mutation , suggesting that these tumors may have different molecular landscaping from general lung adenocarcinoma.

almost 2 years ago

BRCA Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • DDR2 (Discoidin domain receptor 2)

TP53 mutation • KRAS mutation • EGFR mutation • MET exon 14 mutation • NF1 mutation • MET mutation • RB1 mutation • RB1 mutation + TP53 mutation

over2years

Dynamic Mutation Profiles of SCLC Transformation in NSCLC Patients Harboring Concurrent EGFR/TP53/RB1 Mutations (IASLC-WCLC 2022)

In LUAD patients with concurrent EGFR/TP53/RB1 mutations, SCLC transformed patients showed different mutation profiles featured by gain of CNVs. The combination of clinical and molecular features might be used to predict SCLC transformation of LUAD.

over 2 years ago

Clinical

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TERT (Telomerase Reverse Transcriptase) • CCNE1 (Cyclin E1) • IL7R (Interleukin 7 Receptor)

TP53 mutation • EGFR mutation • EGFR exon 19 deletion • PTEN mutation • RB1 mutation • EGFR positive • EGFR mutation + PTEN mutation • RB1 mutation + TP53 mutation

over2years

Neuroendocrine transformation from EGFR/ALK-wild type or TKI-naïve non-small cell lung cancer: An under-recognized phenomenon. (PubMed, Lung Cancer)

This proof-of-concept study demonstrated that NET develops in NSCLCs without TKI targets or treatments. This phenomenon could be under-recognized, because re-biopsy was less frequently performed in these patients. Tissue re-biopsy should be preferred over liquid biopsy at the time of progression to account for histology transformation. p53/Rb IHC should be considered in addition to genomic TP53/RB1 evaluation for NET risk prediction.

over 2 years ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

TP53 mutation • EGFR mutation • EGFR wild-type • ALK mutation • ALK wild-type • RB1 mutation • PDGFRA mutation • RB1 mutation + TP53 mutation

over2years

Homologous Recombination Related Signatures Predict Prognosis and Immunotherapy Response in Metastatic Urothelial Carcinoma. (PubMed, Front Genet)

These genes are expressed at significantly higher levels in tumors, high-grade cancer, and invasive cancer than other categories, and are associated with TP53 and RB1 mutations. HR-related genes are upregulated in genomically unstable samples, the survival time of mUC patients after treatment with ICIs can be predicted using a normogram model based on HR signature.

over 2 years ago

Journal • IO biomarker

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • RAD51 (RAD51 Homolog A) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • RAD54L (DNA Repair And Recombination Protein RAD54)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

over2years

KRAS, IN ADDITION TO P53, IS A DRIVER FOR EARLY CARCINOGENESIS AND MOLECULAR TARGET IN A NOVEL MOUSE MODEL OF INVASIVE ESOPHAGEAL ADENOCARCINOMA (DDW 2022)

The induction of single genetic alteration in addition to IL1b induced chronic inflammation in the L2-IL-1b mouse model accelerated tumor formation macroscopically and histopathologic dysplasia scores mostly in L2-LK followed by L2-LP and L2-LR mice. Dual induction of genetic alteration in L2-LPR, L2-LKP and L2-LKR mice further confirmed the accelerating role of KRas especially with development of ≥5mm invasive cancers in combination with a p53 mutation. Finally, the combination of all 3 genetic events in Lgr5+ cells induced invasive and undifferentiated cancer development at the age of 6 month presenting for the first time a mouse model of invasive EAC.

over 2 years ago

Preclinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IL1B (Interleukin 1, beta)

TP53 mutation • KRAS G12D • KRAS G12 • RB1 mutation + TP53 mutation

almost3years

Two distinct transcriptional responses to type II interferon treatment in Merkel cell carcinoma cell lines corresponds to immune infiltrate signatures found in clinical samples and patient overall survival (LCC 2022)

Gene set enrichment analysis testing sig-A and sig-B combined with Cox-regression survival analysis in an expanded patient cohort (n=89) showed better overall survival for those patients with high sig-A enrichment scores (>75th percentile, p=0.003). We therefore demonstrated our MCC cell lines are representative models of VN and VP-MCC and that immune response and patient survival may be associated with an intrinsic cellular program linked to IFNg response in tumour cells.

almost 3 years ago

Preclinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma)

PD-L1 expression • TP53 mutation • TMB-H • PD-L1 overexpression • TMB-L • RB1 mutation • RB1 mutation + TP53 mutation

almost3years

[VIRTUAL] Genomic Profiling of Responders and Nonresponders to Checkpoint Inhibition in Neuroendocrine Carcinoma (NANETS 2021)

In this small series, the small cell lung cancer-like genomic signature of TP53and RB1mutations was significantly more frequent in responders to ICI compared to non-responders. Further study is warranted to determine whether the presence of having simultaneous TP53and RB1mutations predicts response to ICI in NEC.

almost 3 years ago

Checkpoint inhibition • IO biomarker

TP53 (Tumor protein P53) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • RB1 mutation + TP53 mutation

3years

Lineage-restricted neoplasia driven by Myc defaults to small cell lung cancer when combined with loss of p53 and Rb in the airway epithelium. (PubMed, Oncogene)

However, cell of origin influenced disease latency, metastatic potential, and the transcriptional profile of the SCLC phenotype. Together this reveals that MYC overexpression alone provides a proliferative advantage but when combined with deletion of Trp53 and Rb1 it facilitates the formation of aggressive SCLC from multiple cell lineages.

3 years ago

Journal

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1)

TP53 mutation • MYC amplification • MYC overexpression • RB1 deletion • RB1 mutation • MYC expression • TP53 expression • RB1 overexpression • RB1 mutation + TP53 mutation

3years

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas. (PubMed, Int J Mol Sci)

MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.

3 years ago

Journal • Next-generation sequencing

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • KMT2C (Lysine Methyltransferase 2C) • PMS2 (PMS1 protein homolog 2) • PTPRT (Protein tyrosine phosphatase receptor type T) • PCLO (Piccolo Presynaptic Cytomatrix Protein)

TP53 mutation • MYC amplification • RB1 mutation • MYC expression • PMS2 mutation • RB1 mutation + TP53 mutation

3years

Absence of Biomarker-Driven Treatment Options in Small Cell Lung Cancer, and Selected Preclinical Candidates for Next Generation Combination Therapies. (PubMed, Front Pharmacol)

ONC201 activates the cellular integrated stress response and induces the TRAIL pro-apoptotic pathway. Combination treatment of lurbinectedin with ONC201 are currently being investigated in preclinical studies that may facilitate translation into clinical trials for SCLC patients.

3 years ago

Preclinical • Review • Journal • Combination therapy • IO biomarker

TP53 (Tumor protein P53)

TP53 mutation • RB1 mutation + TP53 mutation

Zepzelca (lurbinectedin) • dordaviprone (ONC201)

3years

The effect of the TP53 and RB1 mutations on the survival of hepatocellular carcinoma patients with different racial backgrounds. (PubMed, J Gastrointest Oncol)

Asian HCC patients with the RB1 mutation had a decreased proportion of infiltrating CD8 T cells. The effects of the TP53 and RB1 mutations on survival differ among Asian and Caucasian HCC patients.

3 years ago

Clinical • Journal

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • CD8 (cluster of differentiation 8)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

over3years

Clinicopathological and genomic features in patients with head and neck neuroendocrine carcinoma. (PubMed, Mod Pathol)

The lower TP53 and RB1 mutation prevalence rates compared to those described for small cell lung cancer suggests the biological heterogeneity of NEC in different parts of the body. Furthermore, the FGFR3-TACC3 fusion gene and mutations in genes encoding the components of the NOTCH and PI3K/AKT/mTOR pathways found in our study may be promising targets for NEC of the head and neck.

over 3 years ago

Clinical • Journal • Tumor Mutational Burden

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)

TP53 mutation • FGFR3-TACC3 fusion • RB1 mutation • FGFR3 fusion • RB1 mutation + TP53 mutation

over3years

[VIRTUAL] The value of defining molecular resistance in patients with progressive EGFR and ALK-driven lung cancer in a public system. (ASCO 2021)

The majority, 81% (n = 22) had EGFR mutated NSCLC, and had progressed on EGFR TKIs (15 with previously identified T790M had progressed on osimertinib), and 19% (n = 5) had ALK fusions... Molecular profiling upon development of resistance to targeted therapy in our cohort revealed actionable resistance mechanisms for over a third of patients and clinical trial options for 67% . These incremental benefits for patients highlight the importance of routine molecular profiling in the setting of acquired TKI resistance in lung cancer.

over 3 years ago

Clinical

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1)

TP53 mutation • BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • EGFR C797S • ALK mutation • MET mutation • RB1 mutation • ALK G1202R • ALK I1171N • ALK I1171 • BRAF amplification • RB1 mutation + TP53 mutation

Tagrisso (osimertinib)

over3years

[VIRTUAL] Generation of a Circulating Tumour Cell (CTC)-Derived eXplant of a NeuroEndocrine Carcinoma of unknown origin. (EACR 2021)

CDX generation was successful from a pre-treatment CTC sample from a patient with a metastatic NEC of unknown origin who responded to platinum/etoposide (P/E)...Conclusion Here, we report on the generation of the first CDX of a NEC of unknown origin. This CDX recapitulates the biology of the original donor patient’s tumour, holding the potential to serve as an avatar to guide future treatment of this donor.

over 3 years ago

Circulating tumor cells

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NCAM1 (Neural cell adhesion molecule 1) • EPCAM (Epithelial cell adhesion molecule) • NKX2-1 (NK2 Homeobox 1) • SYP (Synaptophysin) • CHGA (Chromogranin A)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

CELLSEARCH®

etoposide IV

over3years

[VIRTUAL] Analysis of gene landscape of small cell lung cancer of Chinese through next-generation sequencing (AACR 2021)

Chinese patients with SCLC have rich spectrum of gene mutations, it suggests that targeted therapy should also have certain potential. In addition, about half of SCLCs have a TMB level above 10mutants/Mb, and immunotherapy should been considered more in the future treatment for Chinese SCLC patients.

over 3 years ago

Tumor mutational burden • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker • Next-generation sequencing

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RB1 (RB Transcriptional Corepressor 1) • LRP1B (LDL Receptor Related Protein 1B) • MSH2 (MutS Homolog 2) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)

PD-L1 expression • TP53 mutation • PD-L1 negative • RB1 mutation + TP53 mutation

PD-L1 IHC 22C3 pharmDx

almost4years

Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Speciﬁc Molecular Signature. (PubMed, Cells)

"In some cancer types, the C1/C2 classification was associated with survival and drug sensitivity, and modulated the prognostic meaning of the immune infiltrate. Our results suggest that PAM50 could be repurposed for a pan-cancer context when paired with uncertainty assessment, resulting in two classes with molecular, biological, and clinical implications."

almost 4 years ago

Journal • Pan tumor

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)

TP53 mutation • RB1 mutation • RB1 mutation + TP53 mutation

Prosigna™ Breast Cancer Prognostic Gene Signature Assay