News - NF1 mutation - LARVOL VERI

Incidental finding of a pathogenic mosaicism in the NF1 gene detected by near infrared fundus imaging - a case report. (PubMed, Ophthalmic Genet)

The patient was referred for genetic testing and a somatic mosaic mutation was found on the NF1 gene (c.4084C>T on the exon 30) with a variant allele frequency of 20%. This report highlights the role of near infrared reflectance imaging in the incidental finding of choroidal alterations, which led to the diagnosis of NF1 mosaicism.

3 days ago

Journal

NF1 (Neurofibromin 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)

NF1 mutation

Genetic landscape of Romanian PPGLs. (PubMed, J Cell Mol Med)

RET pathogenic variant (p.Cys634Trp) associated with MEN2A syndrome was the most prevalent in Romanian population with PPGLs and could be considered as a founder effect. Patients with hereditary disease are diagnosed at a younger age and develop bilateral tumors more frequently compared to sporadic cases.

4 days ago

Retrospective data • Journal

RET (Ret Proto-Oncogene) • NF1 (Neurofibromin 1) • VHL (von Hippel-Lindau tumor suppressor) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHD (Succinate Dehydrogenase Complex Subunit D)

NF1 mutation • RET mutation • VHL mutation • FANCA mutation • SDHB mutation

11d

Portraying the full picture of Neurofibromatosis-Noonan syndrome: a systematic review of literature. (PubMed, J Med Genet)

Based on our findings, we emphasise on the importance of searching for NS features in patients with NF1 since the prognosis, comorbidities and consequently management could be altered.

11 days ago

Review • Journal

NF1 (Neurofibromin 1)

NF1 mutation

13d

Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy. (PubMed, JCO Precis Oncol)

Considering the occurrence of several actionable alterations including a TPM4:NTRK1 fusion reported herein, these results support the use of next-generation sequencing (NGS) including RNA analysis for fusion detection to identify such alterations in patients with MPTs. These findings highlight the importance of comprehensive NGS in MPT research to uncover potential targeted treatment options for these patients.

13 days ago

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

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NF1 (Neurofibromin 1) • TPM4 (Tropomyosin 4)

TP53 mutation • EGFR mutation • BRAF mutation • HER-2 negative • PIK3CA mutation • NTRK1 fusion • HER-2 expression • NF1 mutation

MI Tumor Seek™

Vitrakvi (larotrectinib)

15d

A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)

P1, N=100, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2024 --> Apr 2025

15 days ago

Enrollment closed • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)

KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative

TAS0612

15d

Uterine sarcoma with KAT6B/A::KANSL1 fusion: a molecular and clinicopathological study on 9 cases. (PubMed, Virchows Arch)

Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

15 days ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • TSC1 (TSC complex subunit 1) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • KAT6B (Lysine Acetyltransferase 6B)

TP53 mutation • ATM mutation • PTEN mutation • NF1 mutation • TSC1 mutation • PDGFRB mutation

19d

Fatal abdominal hemorrhage following surgery to remove a retroperitoneal MPNST associated with NF1: A case report. (PubMed, Medicine (Baltimore))

It is crucial to assess the potential for heterogeneous differentiation in MPNST during pathological diagnosis. In the treatment of MPNST with heterogeneous differentiation, particularly in cases with significant tumor bulk, surgeons must anticipate potential hemorrhagic complications and adopt a cautious approach to surgical intervention.

19 days ago

Journal • Surgery

NF1 (Neurofibromin 1)

NF1 mutation

21d

The Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer. (PubMed, Int J Mol Sci)

This review provides an overview of the mechanisms of FDA-approved immunotherapeutic drugs, offering an updated perspective on the current state and future developments in lung cancer therapy. More importantly, the factors that positively and negatively impact the immunotherapy's efficacy will also be discussed.

21 days ago

Review • Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • ATM mutation • NF1 mutation • KEAP1 mutation

25d

Atypical cellular neurothekeoma: a case report with a novel NF1 mutation. (PubMed, Diagn Pathol)

Additionally, we present a novel heterozygous predicted inactivating NF1 mutation, not previously reported, which was identified using high-throughput molecular techniques. Such finding might provide insights into the pathogenesis of neurothekeoma, potentially contributing to future refinements in diagnosis, which would enable more precise identification of this neoplasm.

25 days ago

Journal

NF1 (Neurofibromin 1)

NF1 mutation

28d

Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan. (PubMed, Cancer Med)

This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

28 days ago

Journal • Tumor mutational burden • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q)

BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • PTEN mutation • BRAF V600K • TMB-L • NF1 mutation

Management of high grade primary cerebellar tumours. (PubMed, J Pak Med Assoc)

Recent studies emphasize the genetic differences between cerebellar and supratentorial tumours, with new treatments targetting specific molecular abnormalities. Immunotherapy has shown limited effectiveness due to the unique tumour environment in cHGG, and further research is required to improve treatment strategies for these rare tumours.

1 month ago

Review • Journal • IO biomarker

NF1 (Neurofibromin 1)

NF1 mutation • RAS mutation

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 month ago

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

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

Liquid biopsy-based comprehensive genomic profiling captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAFV600E wild type metastatic colorectal cancer in the CAPRI 2-GOIM trial (AIOM 2024)

Materials and The phase II CAPRI 2-GOIM trial investigates the efficacy and safety of biomarkerdriven, cetuximab-based, sequence of three treatment lines in mCRC... Baseline plasma-based comprehensive genomic profiling is feasible with high concordance with tissue-based analysis. Liquid biopsy allows identification of misdiagnosed RAS/BRAF alterations and the ultra-selection of pts, which could benefit from anti-EGFR therapies. Finally, potentially actionable gene alterations were found in half of the pts.

1 month ago

Clinical • Late-breaking abstract • Liquid biopsy • Metastases • Biopsy

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus)

BRAF V600E • KRAS mutation • HER-2 amplification • NRAS mutation • BRAF V600 • PTEN mutation • BRAF wild-type • NF1 mutation • EGFR amplification + ERBB2 amplification

FoundationOne® CDx

Erbitux (cetuximab)

Cyclin-Dependent Kinase (CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type I (NF1) Related Atypical Neurofibromas (clinicaltrials.gov)

P1/2, N=55, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2026 --> Dec 2029 | Trial primary completion date: Dec 2025 --> Dec 2028

1 month ago

Trial completion date • Trial primary completion date

NF1 (Neurofibromin 1)

NF1 mutation

Verzenio (abemaciclib)

Study to Evaluate the Safety, Tolerability, PK Characteristics and Anti-tumor Activity of FCN-159 in Adult and Pediatric Participants With Neurofibromatosis Type 1 (clinicaltrials.gov)

P1/2, N=160, Active, not recruiting, Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Phase classification: P2 --> P1/2

1 month ago

Phase classification

NF1 (Neurofibromin 1)

NF1 mutation

luvometinib (FCN-159)

A prospective clinical study to evaluate the efficacy of dexitabine in maintenance therapy after hematopoietic stem cell transplantation in juvenile myelomonocytic leukemia (ChiCTR2400091166)

P=N/A, N=40, Not yet recruiting, The Seventh Affiliated Hospital, Sun Yat-sen University; The Seventh Affiliated Hospital, Sun Yat-sen University

1 month ago

New trial

KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

KRAS mutation • NRAS mutation • NF1 mutation • PTPN11 mutation • CBL mutation

Whole exome tumor molecular profiling from cerebrospinal fluid (CSF): preliminary results of a pilot study (SNO 2024)

These preliminary results suggest that CSF liquid biopsy may be useful for identifying mutations in primary and metastatic brain tumors. Serial sampling is feasible, and may disclose changes in diagnostic and/or driver mutations over time, with important therapeutic and diagnostic implications. Many mutations were found in CSF alone.

1 month ago

Clinical • BRCA Biomarker • IO biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • NF1 (Neurofibromin 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • PIM1 (Pim-1 Proto-Oncogene)

PIK3CA mutation • IDH1 mutation • PTEN mutation • NF1 mutation • BRCA mutation

Caris Assure™

Prospective germline sequencing of patients with gliomas, glioneuronal or neuronal tumors (SNO 2024)

Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.

1 month ago

Clinical • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

TP53 mutation • NF1 mutation • CHEK2 mutation • IDH wild-type

MSK-IMPACT

Whole exome tumor molecular profiling from cerebrospinal fluid (CSF): preliminary results of a pilot study (SNO 2024)

1 month ago

Clinical • BRCA Biomarker • IO biomarker

PIK3CA mutation • IDH1 mutation • PTEN mutation • NF1 mutation • BRCA mutation

Caris Assure™

Neurofibromatosis Type 1 Patients With Epilepsy: A Comprehensive Analysis of Demographics, Comorbidities and Healthcare Outcomes. (PubMed, Exp Dermatol)

Multivariable logistic regression revealed that malignant brain neoplasms, paralytic ileus, scoliosis, pregnancy complications, paralysis, other neurological disorders, metastatic cancer, coagulopathy, drug abuse and hypertension were predictors of developing epilepsy in NF1 patients. Additionally, epilepsy in NF1 patients was associated with a shorter length of stay, lower total charges and fewer total procedures.

1 month ago

Retrospective data • Journal

NF1 (Neurofibromin 1)

NF1 mutation

Circulating Tumor DNA Predicts Venous Thromboembolism in Minority Patients with Cancers (ASH 2024)

These findings require external validation, particularly using different ctDNA panels. Further research is needed to elucidate the biological mechanisms underlying the association between specific mutations and VTE risk in cancer patients.

1 month ago

Clinical • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1)

KRAS mutation • EGFR mutation • PTEN mutation • NF1 mutation

Tempus xF Assay

Genetic and clinical characteristics of genetic tumor syndromes in the central nervous system cancers: Implications for clinical practice. (PubMed, iScience)

The top five GTS in CNS tumors showed high genetic heterogeneity GTS analysis reclassifies CNS tumors as "NEC." 53.88% of patients diagnosed with GTS harbor potential precision oncology therapy target mutations. The results of our study deepen our understanding of CNS tumors, provide a reference direction for the future design of clinical trials, and further expect to improve disease entire process management in CNS tumors.

1 month ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • MSH2 (MutS Homolog 2)

TP53 mutation • NF1 mutation • MSH2 mutation

2ms

TSPO deficiency promotes the progression of malignant peripheral sheath tumors by regulating the G2/M phase of the cell cycle via CDK1. (PubMed, Sci Rep)

More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.

2 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • NF1 (Neurofibromin 1) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1) • HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1)

NF1 mutation • CDKN1B expression

2ms

ADVL1521: Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (clinicaltrials.gov)

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

2 months ago

Trial completion date

NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

NF1 mutation • RAS mutation • PTPN11 mutation • CBL mutation

Mekinist (trametinib) • omipalisib (GSK2126458)

2ms

Spine Stereotactic Radiosurgery Provides Long-Term Local Control and Overall Survival for Benign Intradural Tumors. (PubMed, Neurosurgery)

With long-term follow-up, spine radiosurgery is a safe and effective treatment for benign intradural tumors. In carefully selected patients, even with an NF1 mutation, SRS is associated with a high likelihood of local tumor control.

2 months ago

Journal • Surgery

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Several suggestions for improving diagnosis and management of patients with neurofibromatosis type 1 (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)

In this paper, we reviewed the current status of comprehensive diagnosis and treatment of NF1 in China, combine with our long-term experiences in diagnosis and treatment of this disease. Meanwhile, we propose future directions and several suggestions for the comprehensive diagnosis and treatment model for Chinese NF1 patients.

2 months ago

Review • Journal

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Progress and prospects in diagnosis and treatment of neurofibromatosis type 1 (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)

However, due to the complexity of the disease and the lack of effective treatments, the diagnosis and treatment of NF1 still face many challenges. Strengthening multidisciplinary collaboration, improving and popularizing disease diagnosis and treatment strategies, and developing more effective drugs and treatment methods are the keys to further improve the treatment level of NF1 diseases.

2 months ago

Review • Journal

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Circulating tumor DNA in conjunctival melanoma: landscape and surveillance value. (PubMed, Am J Ophthalmol)

Positive plasma ctDNA reflected the presence of metastases. The ctDNA could be used as a complement or alternative to tissue sequencing. High VAF ctDNA might indicate rapid disease progression in distant metastasis patients.

2 months ago

Journal • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • NF1 mutation

2ms

Sporadic NF1-Mutated Inflammatory Polyps of the Colon: A Case Report and Brief Literature Review. (PubMed, Genes Chromosomes Cancer)

No abstract available

2 months ago

Review • Journal

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Mesenchymal-type genetic mutations are likely pre-requisite for glioblastoma multiforme to metastasize outside the central nervous system: an original case series and systematic review of the literature. (PubMed, World Neurosurg)

In sum, there is strong evidence that GBMs acquire novel mutations to survive outside the CNS. In some cases, tumor cells likely mutate after seeding scalp tissue during surgery, and in others, they mutate and spread without surgery. Future studies and genetic profiling of primary and metastatic lesions may help uncover the mechanisms of spread.

2 months ago

Review • Journal • Metastases

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • VIM (Vimentin)

TP53 mutation • PTEN mutation • NF1 mutation • TERT mutation • VIM expression • CDK4 mutation

2ms

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=53, Terminated, Pfizer | Trial completion date: Nov 2025 --> Jun 2024 | Active, not recruiting --> Terminated; The study was prematurely discontinued due to strategic reasons, not major safety concerns, futility, or requests from any regulatory authorities

2 months ago

Trial completion date • Trial termination • Combination therapy • Metastases

ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NF1 (Neurofibromin 1)

BRAF V600E • EGFR mutation • BRAF V600 • ALK positive • NF1 mutation • RAS mutation • ROS1 positive

Erbitux (cetuximab) • Lorbrena (lorlatinib) • Mektovi (binimetinib) • Braftovi (encorafenib) • PF-07284892

2ms

cNF Natural Hx: Natural History Study of Cutaneous Neurofibromas in People With NF1 (clinicaltrials.gov)

P=N/A, N=500, Active, not recruiting, Johns Hopkins University | Recruiting --> Active, not recruiting | Trial completion date: Jun 2028 --> Jun 2029 | Trial primary completion date: Dec 2027 --> Dec 2028

2 months ago

Enrollment closed • Trial completion date • Trial primary completion date

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Clinical utility of liquid-based comprehensive genomic profiling (CGP) in gastrointestinal stromal tumors (GIST) (DGHO 2024)

55% (42/77) of liquid samples with a KIT -driver mutation had a co-occurring imatinib-resistant alteration, and a minority of cases harbored non- KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations... Known driver and TKI-resistant mutations are identified in liquid biopsies of patients with GIST, with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification of GIST during the medical management of advanced disease.

2 months ago

Clinical • Stroma

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1)

KIT mutation • FGFR2 mutation • FGFR2 fusion • NF1 mutation • KIT exon 13 mutation • KIT exon 17 mutation

FoundationOne® CDx • FoundationOne® Liquid CDx

imatinib

2ms

Vascular Abnormalities and Neurofibromatosis Type 1: A Paediatric Case Series. (PubMed, J Child Neurol)

Stenosis of the renal artery is another frequent complication of neurofibromatosis type 1, and it represents the most common cause of secondary hypertension in these patients. The purpose of the article is to describe the clinical manifestations of neurofibromatosis type 1 vasculopathy in 4 patients presenting with a wide range of neurologic and reno-vascular manifestations, as well as to examine current diagnostic management and follow-up, current therapeutic options, and to discuss further perspectives in terms of screening, diagnosis, and treatment.

2 months ago

Journal

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Molecular markers for pediatric low-grade glioma. (PubMed, Childs Nerv Syst)

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.

2 months 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

2ms

Identification of Pathogenic Missense Mutations of NF1 Using Computational Approaches. (PubMed, J Mol Neurosci)

Furthermore, to directly visualize the impact of these mutations on protein structure, we utilized AlphaFold3 to simulate both the wild-type and mutant NF1 structures, revealing the significant effects of the R1000C mutation on the protein's conformation. In conclusion, the identification of these mutations can play a pivotal role in advancing the field of precision medicine and aid in the development of effective drugs for associated diseases.

2 months ago

Journal

NF1 (Neurofibromin 1)

NF1 mutation

2ms

Identifying Novel Genetic Markers in Pediatric Rhabdomyosarcoma. (PubMed, J Pediatr Surg)

In patients with at least one mutation in BCOR, NF1, TP53, KRAS, HRAS, or CTNNB1, later age of onset is associated with poorer prognosis. In patients with mutations only in tumor suppressor genes BCOR or NF1, later age of onset is associated with poorer prognosis.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • FGFR4 (Fibroblast growth factor receptor 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • BCOR (BCL6 Corepressor)

TP53 mutation • KRAS mutation • NRAS mutation • NF1 mutation • HRAS mutation • BCOR mutation

2ms

Cancer risk assessment of premalignant breast tissues from patients with BRCA mutations by genome profiling. (PubMed, NPJ Breast Cancer)

Additional WES on 42 samples with relatively large clone size (VAF > 3%) confirmed that these cell clones harbored multiple mutations (10.7 mutations/sample), and the number of existing mutations was consistent with the clone size (R = 0.50). The results suggest that clonal changes occur in normal breast tissue of women at high risk for breast cancer even before cancer is detected pathologically and/or radiologically, and the clonality score shows the potential to be a valid method of evaluating clonal expansion for cancer-risk assessment that provides appropriate preventive options for patients at high risk for breast cancer.

2 months ago

Journal • BRCA Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • BRCA (Breast cancer early onset)

PIK3CA mutation • NF1 mutation • HRAS mutation • BRCA mutation

3ms

Circulating tumor DNA predicts venous thromboembolism in patients with cancers. (PubMed, J Thromb Haemost)

CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management.

3 months ago

Journal • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1)

KRAS mutation • EGFR mutation • PTEN mutation • NF1 mutation

3ms

Whole-Exome Sequencing Reveals Novel Candidate Driver Mutations and Potential Druggable Mutations in Patients with High-Risk Neuroblastoma. (PubMed, J Pers Med)

We also identified 11 putative actionable mutations including NF1 Q1798*, Q2616*, and S636X, ALK F1174L and R1275Q, SETD2 P10L and Q1829E, BRCA1 R612S, NOTCH1 D1670V, ATR S1372L, and FGFR1 N577K. Our findings provide a comprehensive overview of the novel information relevant to the underlying molecular pathogenesis and therapeutic targets of neuroblastoma.

3 months ago

Journal • BRCA Biomarker

ALK (Anaplastic lymphoma kinase) • BRCA1 (Breast cancer 1, early onset) • FGFR1 (Fibroblast growth factor receptor 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • MUC16 (Mucin 16, Cell Surface Associated) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MUC4 (Mucin 4, Cell Surface Associated) • CTNND1 (Catenin Delta 1)

NF1 mutation • MUC16 mutation • ALK R1275Q

3ms

Cold Atmospheric Plasma Induces Growth Arrest and Apoptosis in Neurofibromatosis Type 1-Associated Peripheral Nerve Sheath Tumor Cells. (PubMed, Biomedicines)

Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.

3 months ago

Journal • Tumor cell

NF1 (Neurofibromin 1)

NF1 mutation

3ms

Generation of an induced pluripotent stem cell line from a type 1 neurofibromatosis patient with NF1 mutation. (PubMed, Stem Cell Res)

The iPSC line expresses pluripotency markers, displays a normal karyotype, and is able to differentiate into three germ layers in vitro. This iPSC line represents a valuable cell model for NF1 in humans.

3 months ago

Preclinical • Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NF1 (Neurofibromin 1) • BCL2L1 (BCL2-like 1) • SOX2 • POU5F1 (POU Class 5 Homeobox 1)

NF1 mutation • MYC expression