Accordingly, comprehensive molecular profiling-specifically genetic sequencing, often plus copy number profiling-has become critical for guiding the diagnosis and management of PLGG. In this review, we discuss the most important genetic alterations that inform on classification and prognosis of PLGG, highlighting their diagnostic and therapeutic relevance.

1 year ago

Journal

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler)

BRAF mutation • NF1 mutation • FGFR1 fusion

1year

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case. (PubMed, J Neurosurg Case Lessons)

Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

1 year ago

Journal

FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)

CDKN2A deletion • FGFR1 fusion • FGFR1-TACC1 fusion

1year

Expanding the Molecular Spectrum of Carcinoma Ex Pleomorphic Adenoma: An Analysis of 84 Cases With a Novel HMGA2::LINC02389 Fusion. (PubMed, Am J Surg Pathol)

A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.

1 year ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • EWSR1 (EWS RNA Binding Protein 1) • LIFR (LIF Receptor Subunit Alpha) • HMGA2 (High mobility group AT-hook 2) • PLAG1 (PLAG1 Zinc Finger)

TP53 mutation • HER-2 amplification • PTEN mutation • HRAS mutation • FGFR1 fusion

1year

FGFR2-fusions define a clinically actionable molecular subset of pancreatic cancer. (PubMed, NPJ Precis Oncol)

FGFR fusions were generally mutually exclusive from other known oncogenes. Our findings provide clinical evidence for identifying and treating FGFR2 fusion-positive PDAC patients with FGFR targeted therapy.

1 year ago

Journal

FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)

FGFR2 fusion • FGFR fusion • FGFR1 fusion

1year

CD34-positive spindle cell tumour with FGFR1::TACC1 fusion: entity of uncertain behaviour (ECP 2024)

In this particular case, the immunohistochemical and molecular results support a diagnosis of a fibroblastic/myofibroblastic tumour of uncertain behaviour. Notably, there have been no reported cases in the literature of a soft tissue tumour harboring FGFR1::TACC1 fusion as a primary occurrence in this anatomical location. The patient remains in good health without any evidence of disease recurrence at the 5-month follow-up post-surgical intervention.

1 year ago

ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MDM2 (E3 ubiquitin protein ligase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase) • COL1A1 (Collagen Type I Alpha 1 Chain) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)

MDM2 amplification • FGFR1 fusion • CD34 positive

Archer® FusionPlex® Sarcoma kit • FusionPlex® Dx

1year

Emerging Tumor-Agnostic Molecular Targets. (PubMed, Mol Cancer Ther)

Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK, mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (Class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.

1 year ago

Journal • Pan tumor

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • NRG1 (Neuregulin 1)

TP53 mutation • KRAS mutation • KRAS G12C • BRAF mutation • FGFR2 mutation • FGFR2 fusion • ALK fusion • ALK mutation • NRG1 fusion • KRAS G12 • FGFR1 fusion • TP53 Y220C

over1year

Evaluating Debio 1347 in Patients with FGFR Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter, Open-Label, Phase II Basket Trial. (PubMed, Clin Cancer Res)

Debio 1347 had manageable toxicity; however, the efficacy in patients with tumors harboring FGFR fusions did not support further clinical evaluation in this setting. Our transcriptomic-based analysis characterized in detail the incidence and nature of FGFR fusions across solid tumors.

over 1 year ago

P2 data • Journal • Pan tumor • Metastases

FGFR (Fibroblast Growth Factor Receptor)

FGFR fusion • FGFR1 fusion

zoligratinib (Debio 1347)

over1year

Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors. (PubMed, Cancers (Basel))

Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

over 1 year ago

Journal • Next-generation sequencing • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • BRAF V600E • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FANCA mutation • FGFR1 fusion • FANCA deletion • PDGFR wild-type

imatinib

over1year

Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma (clinicaltrials.gov)

P2, N=55, Completed, TransThera Sciences (Nanjing), Inc. | Active, not recruiting --> Completed

over 1 year ago

Trial completion • Metastases

FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor)

FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR1 mutation • FGFR1 fusion • FGFR wild-type

tinengotinib (TT-00420)

over1year

FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma. (PubMed, Genes Chromosomes Cancer)

However, it remains unclear if FGFR1 fusions define a novel subset of RMS or alternatively, whether this alteration can sporadically drive the pathogenesis of known RMS subtypes, such as ERMS. Additional larger series with integrated genomic and epigenetic datasets are needed for better subclassification, as the resulting oncogenic kinase activation underscores the potential for targeted therapy.

over 1 year ago

Journal

TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • DICER1 (Dicer 1 Ribonuclease III) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1) • NCOA2 (Nuclear Receptor Coactivator 2) • PAX3 (Paired Box 3)

TP53 mutation • FGFR1 overexpression • TET2 mutation • FGFR1 fusion