Analysis of AML with t(4; 12)(q12; p13) translocation by WGS and WTS provides detailed information that separates two subsets distinguished by distinct breakpoint cluster regions on 4q12 and PDGFRA gene expression. The clinical impact of increased PDGFRA gene expression on response to TKI and prognosis as well as the presence of additional fusion transcripts has to be evaluated in further studies.

2 years ago

Clinical • Omic analysis

BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ASXL1 (ASXL Transcriptional Regulator 1) • ETV6 (ETS Variant Transcription Factor 6) • ADAMTS3 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 3) • SCFD2 (Sec1 Family Domain Containing 2)

ASXL1 mutation • PDGFRA mutation • PDGFRA overexpression • PDGFRA fusion

2years

NATRON: A Phase III Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (clinicaltrials.gov)

P3, N=120, Recruiting, AstraZeneca | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2023 --> May 2024

2 years ago

Trial completion date • Trial primary completion date

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

2years

Integration of genomic sequencing drives therapeutic targeting of PDGFRA in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma. (PubMed, Clin Cancer Res)

Refractory T-ALL has not been fully characterized. Alterations in PDGFRA or other targetable kinases may inform therapy for patients with refractory T-ALL who otherwise have limited treatment options. Clinical genomic profiling, in real time, is needed for fully informed therapeutic decision making.

2 years ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

PDGFRA mutation • PDGFRA fusion

Ayvakit (avapritinib)

2years

Gliomas in adolescents and young adults – experience of cases presented at national AYA multi-disciplinary rounds (SNO 2023)

Within national rounds, there was enrichment of pediatric-type tumors and patients with cancer predisposition syndromes. Targeted agents are available for many of these driver mutations with potential improved outcomes; however, access to these agents in AYA may be limited. Clinicians face complex management questions in this population and underscores the need for a multi-disciplinary approach along with clinical trial opportunities for these patients.

2 years ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)

IDH wild-type • NTRK fusion • PDGFRA fusion

2years

Implementing genomic profiling as standard-of-care for glioblastoma patients. (SNO 2023)

Genomic profiling revealed actionable targets and new therapeutic options for glioblastoma pts. A full and updated overview of patient characteristics, actionable targets and survival data will be presented at the meeting.

2 years ago

Clinical

TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • TMB-H • FGFR mutation • FGFR fusion • MET mutation • PDGFRA mutation • NTRK fusion • PDGFRA fusion

2years

Utility of Next-Generation Sequencing in the Detection of RNA Fusion Genes in Myeloid Malignancies in Singapore (ASH 2023)

Conclusion We have demonstrated that NGS has a high sensitivity for identification of RNA fusion genes, is complementary to conventional cytogenetics testing, and has vast clinical impact in terms of diagnosis, prognostication and clinical management. We advocate for the integration of NGS with DNA and RNA sequencing into routine investigation of suspected myeloid malignancies for a more precise and comprehensive diagnostic approach.

2 years ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PML (Promyelocytic Leukemia) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • DEK (DEK Proto-Oncogene)

FLT3-ITD mutation • BCR-ABL1 fusion • NF1 mutation • ASXL1 mutation • U2AF1 mutation • CBFB-MYH11 fusion • MLL fusion • PDGFRA fusion

Oncomine Myeloid Research Assay

2years

RNA Fusions and Their Association with DNA Alterations in Myeloid Neoplasia Patients Identified By a Single Tube Multimodal Comprehensive Genomic Profiling Test (ASH 2023)

A robust low-noise RNA fusion detection assay coupled us DNA alterations on myeloid disorders in a single assay enables to fully molecularly characterize acute myeloid leukemias and other myeloid disorders. Frequencies of well-known fusions in a small community-based cohort were similar to studies performed in academic settings with subsets of gene alterations being mutually exclusive from fusions. Larger studies are needed to confirm those associations.

2 years ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • NPM1 (Nucleophosmin 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • CCND2 (Cyclin D2) • PHF6 (PHD Finger Protein 6) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • ZNF384 (Zinc Finger Protein 384)

FGFR1 fusion • ABL1 fusion • PDGFRA fusion

2years

AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)

P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Initiation date: Apr 2023 --> Sep 2023

2 years ago

Trial initiation date • Combination therapy • Metastases

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion

azacitidine • elenestinib (BLU-263)

over2years

The landscape of PDGFRA mutation in Chinese patients with glioma (ESMO 2023)

This type of mutation is mostly found in the non-tyrosine kinase domain. Investigating the PDGFRA map and PDGFRA inhibitors has significant exploratory value.

over 2 years ago

Clinical

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA D842V • PDGFRA mutation • KIT fusion • PDGFRA fusion