News - FGF3 amplification

2ms

Point mutations (PM), gene amplifications (GA) and variants of unknown significance (VUS) detected by next-generation sequencing (NGS) in a real-world sample of metastatic breast cancer (MBC) (SABCS 2024)

NGS of real-world patients reveals a broad spectrum of genomic abnormalities in MBC. TP53 and PIK3CA associate with TNBC and luminal MBC, respectively. Mutations in tumor suppressors are mostly distinct since there are many ways to induce loss-of-function.

2 months ago

Clinical • Real-world evidence • Next-generation sequencing • MSi-H Biomarker • Real-world • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1) • FGF4 (Fibroblast growth factor 4) • AURKA (Aurora kinase A) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • GNAS (GNAS Complex Locus) • CCND2 (Cyclin D2) • RAD21 (RAD21 Cohesin Complex Component) • KDM5A (Lysine Demethylase 5A) • ZNF217 (Zinc Finger Protein 217) • FGF23 (Fibroblast Growth Factor 23) • GATA3 (GATA binding protein 3) • ZNF703 (Zinc Finger Protein 703)

TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • FGFR1 amplification • CCND1 amplification • FGF3 amplification

Guardant360® CDx

10ms

Feasibility and clinical utility of blood based NGS in head and neck carcinomas : A single center experience from precision medicine program. (AACR 2024)

This study demonstrates the feasibility of liquid biopsy in HNSCC and rare head and neck tumors, providing valuable therapeutic and prognostic insights. The findings underscore the potential of liquid biopsy as a valuable tool in clinical decision-making for head and neck cancer patients.

10 months ago

Clinical • Next-generation sequencing

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • ASXL1 (ASXL Transcriptional Regulator 1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • CHEK2 (Checkpoint kinase 2) • STING (stimulator of interferon response cGAMP interactor 1)

TP53 mutation • PIK3CA mutation • NOTCH1 mutation • FGF3 amplification

FoundationOne® Liquid CDx

over1year

Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers. (PubMed, Cancer)

Penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy in the advanced setting, with poor prognosis and little success with immune-checkpoint inhibitors (ICIs) in an unselected patient approach. Human papillomavirus (HPV) infection is a known risk factor for pSCC; its impact on genomic tumor profiling is less defined. Using next-generation sequencing, we explored the genetic landscape and ICI-related biomarkers of pSCC and HPV-driven oncogenic molecular signatures. Our results indicate that HPV-positive and HPV-negative pSCCs are molecularly distinct tumors. Increased tumor mutational burden is associated with HPV-positive tumors, and could serve as a biomarker for predicting therapeutic response to ICI-based therapies. Our results support the growing literature indicating that HPV status in pSCC can be used to guide patient stratification in ICI-based clinical trials.

over 1 year ago

Checkpoint inhibition • Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H 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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3)

PD-L1 expression • TMB-H • MSI-H/dMMR • PIK3CA mutation • CDKN2A mutation • KMT2C mutation • FGF3 amplification • MLL3 mutation

VENTANA PD-L1 (SP142) Assay

over1year

Clinical Application of Liquid Biopsy across Pan- Cancer: 4baseCare's Experience Using TarGT Indiegene- Liquid Biopsy NGS Panel (AMP Europe 2023)

The MRD estimation was evident in a breast cancer patient with ERBB2 amplification detected while the patient was on maintenance trastuzumab... This pan- cancer pilot study using the TarGT Indiegene Liquid Biopsy Panel supports the hypothesis that molecular information obtained from liquid biopsy can play a significant role in clinical decision-making, in addition to tissue mutation profiling. The results of this study demonstrate the potential clinical utility of this liquid biopsy panel in identifying actionable genomic alterations in patients with advanced stage cancer. These findings suggest that liquid biopsy has the potential to complement tissue biopsy and provide important molecular information to inform personalized treatment decisions for patients with cancer.

over 1 year ago

Clinical • Liquid biopsy • Next-generation sequencing • Biopsy

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • BICC1 (BicC Family RNA Binding Protein 1)

HER-2 amplification • PIK3CA mutation • FGFR2 fusion • CCND1 amplification • FGF3 amplification

Herceptin (trastuzumab)

over2years

LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC. (PubMed, Front Pharmacol)

Mechanistically, FGFs/CCND1 activated the MAPK pathway, which was abolished by the combination drugs. Our study provides a rationale for clinical testing of dual targeting FGFR and CCND1 with LY2874455 and abemaciclib in NSCLC patients who harbored FGF3/4/19/CCND1 amplification.

over 2 years ago

Journal

CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • FGF3 (Fibroblast growth factor 3)

CCND1 amplification • FGF3 amplification

gefitinib • Verzenio (abemaciclib) • LY2874455

over2years

Molecular characterization of KRAS wild type tumors in patients with pancreatic adenocarcinoma. (PubMed, Clin Cancer Res)

KRAS-WT PDAC represents 10.7% of PDAC and is enriched with targetable alterations, including immuno-oncologic markers. Identification of KRAS-WT patients in clinical practice may expand therapeutic options in a clinically meaningful manner.

over 2 years ago

Journal • Tumor Mutational Burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • CD8 (cluster of differentiation 8) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • KMT2C (Lysine Methyltransferase 2C) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • RAD50 (RAD50 Double Strand Break Repair Protein) • ARID2 (AT-Rich Interaction Domain 2) • NTRK (Neurotrophic receptor tyrosine kinase)

PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • BRAF mutation • HER-2 amplification • ATM mutation • PALB2 mutation • KRAS wild-type • FGFR2 fusion • ALK fusion • RAS wild-type • PBRM1 mutation • BAP1 mutation • FGFR3 fusion • RAD50 mutation • FGF3 amplification • HER-2 amplification + PD-L1 expression • KRAS expression

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin

over2years

EGFR Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous Cell Carcinoma. (PubMed, Front Immunol)

Chromosome 11q13 amplification and EGFR mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.

over 2 years ago

Journal • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)

EGFR mutation • CCND1 amplification • FGF3 amplification

almost3years

Clinical implication of plasma ctDNA features in HER2-positive gastric cancer treated with combinations of trastuzumab & anti-PD-1 agents (AACR 2022)

The ctDNA display a high consistency with tumor tissue for HER2 status. Compared to chemo-free regimens, chemo-containing regimens trend to demonstrate improved PFS and ORR in HER2-postive GC/GEJ, though no statistically significant. The HER2 amplification and immune-related negative gene alterations in ctDNA might be used as alternative biomarkers for predicting the efficacy of combining therapeutics containing trastuzumab and anti-PD-1 agents.

almost 3 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker • Circulating tumor DNA

HER-2 (Human epidermal growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • MDM2 (E3 ubiquitin protein ligase) • FGF3 (Fibroblast growth factor 3)

HER-2 positive • HER-2 amplification • PTEN mutation • MDM2 amplification • MDM2 mutation • FGF3 amplification

Herceptin (trastuzumab)

almost3years

Comprehensive genomic proﬁling of penile squamous cell carcinoma and impact of HPV status on immune-checkpoint inhibition-related biomarkers. (ASCO-GU 2022)

"To our knowledge, our comprehensive NGS study of penile SCC somatic alterations is the largest to date. HPV16/18+ vs HPV16/18- penile SCC were molecularly distinct tumors, consistent with previous reports. Our finding that TMB-high was exclusive to patients with HPV16/18+ tumors requires confirmation in larger datasets and could be used for better patient stratification in ICI clinical trials."

almost 3 years ago

Checkpoint inhibition

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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3)

PD-L1 expression • TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • CDKN2A mutation • KMT2C mutation • FGF3 amplification • MLL3 mutation

VENTANA PD-L1 (SP142) Assay

almost3years

Comprehensive genomic proﬁling of penile squamous cell carcinoma and impact of HPV status on immune-checkpoint inhibition-related biomarkers. (ASCO-GU 2022)

almost 3 years ago

Checkpoint inhibition

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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3)

PD-L1 expression • TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • CDKN2A mutation • KMT2C mutation • FGF3 amplification • MLL3 mutation

VENTANA PD-L1 (SP142) Assay

over3years

A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer (clinicaltrials.gov)

P1/2, N=10, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

over 3 years ago

Clinical • Trial completion

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • FGFR (Fibroblast Growth Factor Receptor) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3)

HR positive • HER-2 amplification • HER-2 negative • CCND1 amplification • PGR positive • FGF3 amplification

fulvestrant • zoligratinib (Debio 1347)

over3years

[VIRTUAL] Study on possible mechanisms of HPD associated with the amplification of chromosome 11q13 in NSCLC (ESMO 2021)

The underlying explanation may be related to insufficient infiltration of immune cells, especially M1 macrophages and NK cells.

over 3 years ago

Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3)

PD-L1 expression • TMB-H • CCND1 amplification • FGF3 amplification

PD-L1 IHC 22C3 pharmDx

4years

A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer (clinicaltrials.gov)

P1/2, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2020 --> Nov 2021 | Trial primary completion date: Nov 2020 --> Nov 2021

4 years ago

Clinical • Trial completion date • Trial primary completion date

HR positive • HER-2 amplification • HER-2 negative • CCND1 amplification • PGR positive • FGF3 amplification

fulvestrant • zoligratinib (Debio 1347)

4years

[VIRTUAL] A Dramatic Change in Histopathologic Features of Melanoma After PD1 Blockade: Development of Bizarre-looking Cells (ASDP 2020)

She received one cycle of adjuvant therapy with pembrolizumab, but developed rapid progression of her melanoma both subjectively and on PET scan...Six months later she initiated trametinib but discontinued this due to intolerance...Updated genomic sequencing is pending, but tumor samples in patients with HPD typically demonstrate an increased mutation load compared to before ICI therapy. The histopathologic changes associated with HPD have not been well documented; this case suggests that dramatic alterations in cell cytology may also be a feature of hyperprogressive disease.

4 years ago

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

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MDM2 (E3 ubiquitin protein ligase) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • MDM4 (The mouse double minute 4) • FGF4 (Fibroblast growth factor 4)

PD-L1 expression • BRAF mutation • NRAS mutation • NF1 mutation • NRAS G12 • FGF3 amplification

Keytruda (pembrolizumab) • Mekinist (trametinib)

over4years

A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer (clinicaltrials.gov)

P1/2, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=55 --> 10

over 4 years ago

Clinical • Enrollment closed • Enrollment change

HR positive • HER-2 amplification • HER-2 negative • CCND1 amplification • PGR positive • FGF3 amplification

fulvestrant • zoligratinib (Debio 1347)

over4years

Acquired FGFR and FGF alterations confer resistance to estrogen receptor (ER) targeted therapy in ER+ metastatic breast cancer. (PubMed, Clin Cancer Res)

Our results suggest that FGFR pathway is a distinct mechanism of acquired resistance to ER-directed therapy that can be overcome by FGFR and/or MAPK pathway inhibitors.

over 4 years ago

Journal

ER (Estrogen receptor) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • FGF3 (Fibroblast growth factor 3) • IR (Insulin receptor)

FGFR1 amplification • FGFR2 mutation • FGFR2 amplification • FGF3 amplification

Ibrance (palbociclib) • fulvestrant