News - NF2 mutation - LARVOL VERI

2ms

The Investigation of Transcription Factor SOX11 and PITX1 in Predicting Meningioma Clinical Outcomes (ChiCTR2400094780)

P=N/A, N=500, Southwest Hospital; Southwest Hospital

2 months ago

New trial

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TERT (Telomerase Reverse Transcriptase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2) • KLF4 (Kruppel-like factor 4)

CDKN2A deletion • NF2 mutation • TERT mutation • TERT promoter mutation

2ms

Role of NF2 Mutation in the Development of Eleven Different Cancers. (PubMed, Cancers (Basel))

However, future studies remain to be done to further elucidate the role of the Hippo signaling pathway in the carcinogenesis of human NF2-mutant tumors. The findings of this review provide insights into the role of NF2 mutations in cancers, Hippo signaling in NF2-mutant cancers, and current gaps in our knowledge regarding the two.

2 months ago

Review • Journal

NF2 (Neurofibromin 2)

NF2 mutation

2ms

Development and validation of a molecular classifier of meningiomas. (PubMed, Neuro Oncol)

Our DNA methylation-based classifier, which is publicly available for immediate clinical use, recapitulates the biology and outcomes of the original molecular groups as assessed using multiple metrics/platforms that were not used in its training.

2 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

3ms

Therapeutic effect of novel drug candidate, PRG-N-01, on NF2 syndrome-related tumor. (PubMed, Neuro Oncol)

Together, our study provides the rationale and critical data for a prospective clinical trial of PRG-N-01 in NF2-SWN patients indicating PRG-N-01 as a promising candidate for the treatment.

3 months ago

Journal

NF2 (Neurofibromin 2) • TGFB1 (Transforming Growth Factor Beta 1) • POSTN (Periostin)

NF2 mutation

3ms

Phase II Study of Defactinib (VS6063) in Patients With Tumors With NF2 Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U. (PubMed, JCO Precis Oncol)

This protocol did not meet its prespecified primary end point. Defactinib monotherapy had limited clinical activity in this cohort of previously treated patients with solid tumors exhibiting NF2 loss.

3 months ago

P2 data • Journal

NF2 (Neurofibromin 2)

NF2 mutation

defactinib (VS-6063)

4ms

Primary and salvage radiosurgery for neurofibromatosis type 2-associated meningiomas. (PubMed, J Neurosurg)

In this case series, the LTC rates of both primary and salvage SRS exceeded 90%. However, nearly half of the patients required additional SRS for new untreated meningiomas. No significant differences in long-term LTC were found when comparing upfront versus salvage SRS for patients with NF2 meningiomas. These results establish SRS as a valuable and safe option for managing NF2-associated meningiomas.

4 months ago

Journal • Surgery

NF2 (Neurofibromin 2)

NF2 mutation

4ms

Presenting characteristics and clinical outcomes of idiopathic versus neurofibromatosis type 2-associated spinal meningiomas: a retrospective institutional experience. (PubMed, J Neurosurg Spine)

In this study of 166 surgically treated patients with SM, patients with NF2 presented earlier, experienced earlier progression, and experienced progression more frequently compared with those without NF2. Radiographic characteristics of tumors were relatively consistent between groups. While idiopathic SMs remain a relatively benign and highly manageable disease, considering tumor molecular characteristics and broader clinical history is paramount in providing efficacious and individualized patient care.

4 months ago

Clinical data • Retrospective data • Journal

NF2 (Neurofibromin 2)

NF2 mutation

4ms

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.

4 months 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)

5ms

Neurofibromatosis type-2-related schwannomatosis presenting as peripapillary hamartoma: report on a novel NF2 mutation. (PubMed, Ophthalmic Genet)

By the age of three, her vision worsened, and optical coherence tomography showed vitreomacular traction and intraretinal fluid surrounding the lesion. This case underscores the need to consider NF2- SWN in peripapillary hamartoma diagnoses and highlights the importance of genetic testing for early detection and management.

5 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

5ms

Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2. (PubMed, Dis Model Mech)

Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.

5 months ago

Journal

NF1 (Neurofibromin 1) • NF2 (Neurofibromin 2)

NF2 mutation

5ms

Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated Schwann cell proliferation in human. (PubMed, bioRxiv)

Proteomic analyses identified novel interaction partners for Merlin - Arkadia and SKOR2. Our results established a new model in which merlin interacts with Arkadia and SKOR2 and this interaction is required for the proper activation of the SMAD-dependent pathway in TGFβ signaling.

5 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

5ms

Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4. (PubMed, Neurooncol Adv)

In vitro, overexpression of VGLL4 resulted in the downregulation of YAP activity in benign NF2 mutant meningioma cells, confirming the direct link between VGLL4 expression and decreased levels of YAP activity observed in aggressive NF2 mutant meningiomas. Our results shed new insight into the biology of benign and aggressive NF2 mutant meningiomas and may have important implications for the efficacy of therapies targeting oncogenic YAP1 activity in NF2 mutant meningiomas.

5 months ago

Journal

NF2 (Neurofibromin 2) • YAP1 (Yes associated protein 1) • FAT3 (FAT Atypical Cadherin 3) • VGLL4 (Vestigial Like Family Member 4)

NF2 mutation

5ms

SEL-TH-1601: Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors (clinicaltrials.gov)

P2, N=10, Completed, Children's Hospital Medical Center, Cincinnati | Suspended --> Completed | Trial completion date: Jun 2025 --> May 2024 | Trial primary completion date: Dec 2024 --> May 2024

5 months ago

Trial completion • Trial completion date • Trial primary completion date

NF2 (Neurofibromin 2)

NF2 mutation

Koselugo (selumetinib)

6ms

Blood and cerebrospinal fluid biomarkers in neuro-oncology. (PubMed, Curr Opin Neurol)

This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors.

6 months ago

Journal

PTEN (Phosphatase and tensin homolog) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TERT (Telomerase Reverse Transcriptase) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SMO (Smoothened Frizzled Class Receptor) • KLF4 (Kruppel-like factor 4)

EGFR mutation • PTEN mutation • MYD88 L265P • NF2 mutation • TERT mutation • SMO mutation • TERT promoter mutation

6ms

The actin-binding protein drebrin disrupts NF2-LATS kinases complex assembly to facilitate liver tumorigenesis. (PubMed, Hepatology)

Our study identifies a novel DBN1-NF2-LATS axis, and pharmacological inhibition of DBN1 represents a promising alternative intervention targeting the Hippo pathway in cancer treatment.

6 months ago

Journal

NF1 (Neurofibromin 1) • NF2 (Neurofibromin 2) • LATS1 (Large Tumor Suppressor Kinase 1) • DBN1 (Drebrin 1)

NF2 mutation

sorafenib

6ms

A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients with Progressive Meningiomas (clinicaltrials.gov)

P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Oct 2024 --> Jan 2028 | Trial primary completion date: Oct 2024 --> Jan 2026

6 months ago

Trial completion date • Trial primary completion date

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PTCH1 (Patched 1) • CDK4 (Cyclin-dependent kinase 4) • NF2 (Neurofibromin 2) • SMO (Smoothened Frizzled Class Receptor) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)

PIK3CA mutation • PTEN mutation • CDKN2A mutation • PTCH1 mutation • NF2 mutation • AKT1 mutation • SMO mutation • PIK3CA mutation + PTEN mutation • CDK4 mutation

Verzenio (abemaciclib) • Truqap (capivasertib) • Erivedge (vismodegib) • GSK2256098

10ms

Gene Therapy for Neurofibromatosis Type 2-Related Schwannomatosis: Recent Progress, Challenges, and Future Directions. (PubMed, Oncol Ther)

Gene therapy, which has made significant advancements in treating genetic diseases, holds promise for the treatment of this disease. This review covers the genetic pathogenesis of NF2-related schwannomatosis, the latest progress in gene therapy strategies, current challenges, and future directions of gene therapy for NF2-related schwannomatosis.

10 months ago

Review • Journal • Gene therapy

NF2 (Neurofibromin 2)

NF2 mutation

10ms

Genome-Wide CRISPR Screen Identifies an NF2-Adherens Junction Mechanistic Dependency for Cardiac Lineage. (PubMed, Circulation)

Mechanistically, cardiomyocyte lineage identity was rescued by wild-type and NF2 serine-518 phosphomutants, but not NF2 FERM (ezrin-radixin-meosin homology protein) domain blue-box mutants, demonstrating that the critical FERM domain-dependent formation of the AMOT-NF2-YAP scaffold complex at the adherens junction is required for early cardiomyocyte lineage differentiation. These results provide mechanistic insight into the essential role of NF2 during early epithelial-mesenchymal transition by sequestering the repressive effect of YAP and relieving regulatory roadblocks en route to cardiomyocytes.

10 months ago

Journal

NF1 (Neurofibromin 1) • NF2 (Neurofibromin 2) • SOX2 • EZR (Ezrin) • CDX2 (Caudal Type Homeobox 2) • RDX (Radixin)

NF2 mutation

10ms

Malignant perineurioma derived from the retroperitoneum with an aggressive clinical course: a case report. (PubMed, Surg Case Rep)

This rare case highlights the challenges in managing retroperitoneal malignant perineuriomas. The aggressive characteristics and limited treatment options for advanced malignant perineuriomas underscore the need for understanding the pathogenesis and developing effective systemic therapies. The identification of an NF2 mutation provides significant insights into potential therapeutic target.

10 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

10ms

Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors Enriched for Tumors With NF2 or mNF2 Gene Mutations (clinicaltrials.gov)

P1/2, N=250, Recruiting, Vivace Therapeutics, Inc | Phase classification: P1 --> P1/2 | N=188 --> 250 | Trial completion date: Dec 2024 --> Jun 2027 | Trial primary completion date: Nov 2024 --> Dec 2026

10 months ago

Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Metastases

NF2 (Neurofibromin 2)

NF2 mutation

VT3989

11ms

Sporadic pediatric vestibular schwannoma: a case report in a 4-year-old boy. (PubMed, Childs Nerv Syst)

This case highlights the significance of considering the possibility of sporadic VSs, even in very young children. It emphasizes the importance of not overlooking initial symptoms, as they may indicate the presence of a large tumor and could potentially result in delayed diagnosis.

11 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

11ms

Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice. (PubMed, Clin Exp Med)

Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.

11 months ago

Journal • Tumor mutational burden • BRCA Biomarker

TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2)

BAP1 mutation • NF2 mutation

FoundationOne® CDx

11ms

Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model. (PubMed, J Pathol)

Drug synergy was seen using trametinib and rapamycin in combination with entrectinib.

11 months ago

Preclinical • Journal

NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NF2 (Neurofibromin 2) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)

NF2 mutation • NTRK fusion

Mekinist (trametinib) • Rozlytrek (entrectinib) • sirolimus

11ms

Susceptibility-Weighted MRI for Predicting NF-2 Mutations and S100 Protein Expression in Meningiomas. (PubMed, Diagnostics (Basel))

Deep learning features demonstrated a strong predictive capability for S100 protein expression (AUC = 0.85 ± 0.06) and had reasonable success in identifying NF-2 copy number loss (AUC = 0.74 ± 0.05). In conclusion, SWI showed promise in identifying NF-2 copy number loss and S100 protein expression by revealing neovascularization and microcalcification characteristics in meningiomas.

11 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation • NF2 expression

11ms

EAY131-U: Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U) (clinicaltrials.gov)

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

11 months ago

Trial completion date • Trial primary completion date

NF2 (Neurofibromin 2)

NF2 mutation

defactinib (VS-6063)

12ms

Association of frequent NF2 mutations with spinal location predominance and worse outcomes in psammomatous meningiomas. (PubMed, J Neurosurg)

Female sex and spinal location predominance were statistically significant in PMs. NF2 mutation was an independent predictor for worse PFS of PMs. Of note, NF2 mutation was detected in all SPMs but in only 38.46% of CPMs, revealing a significant difference.

12 months ago

Journal

PGR (Progesterone receptor) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NF2 (Neurofibromin 2)

NF2 mutation • PGR expression

12ms

Neurofibromatosis type 2 in the otorhinolaryngological practice (PubMed, Vestn Otorinolaringol)

The importance of the presented observation is that the doctor should assume neurofibromatosis type 2 in a young patient with bilateral vestibular schwannomas. It is necessary to undertake a further examination of this patient, including: skin examination for the identification of characteristic neurofibromas and cafe-au-lait macules, consultation with an ophthalmologist, neurologist, MRI of the brain and spinal cord with contrast, genetic analysis - for timely initiation of therapy that prevents hearing loss and vestibular disorders.

12 months ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

1year

EAY131-U: Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U) (clinicaltrials.gov)

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

1 year ago

Trial completion date

NF2 (Neurofibromin 2)

NF2 mutation

defactinib (VS-6063)

1year

NF2 mutations are enriched in FH deficient renal cell cancer (AACR 2024)

NF2 mutations have been identified in a variety of morphologic types of Renal cell cancer. However, we were surprised by the number of cases with NF2 mutation in tumors that also harbor the FH (HLRCC) mutation. NF2 tumors have been reported to have an aggressive behavior, and FH cancers are also known to have poor survival.

1 year ago

NF2 (Neurofibromin 2) • B2M (Beta-2-microglobulin) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • ARID1B (AT-Rich Interaction Domain 1B) • EP300 (E1A binding protein p300) • BCORL1 (BCL6 Corepressor Like 1)

VHL mutation • NF2 mutation

TruSight Oncology 500 Assay

1year

Molecular profiling using next generation sequencing with high purity enrichment of circulating tumor cells (AACR 2024)

Molecular analysis of CTCs is a challenge since CTCs are very rare in the blood and there are technical limitations in isolating CTCs with sufficient purity. In this study, we developed the process for NGS analysis on very low number of CTCs with high purity, isolated using CytoGen's Smart Biopsyâ„¢ system. Overall, these process could provide information for diagnosis and appropriate treatment of metastatic breast cancer along with the results of our ongoing clinical trials.

1 year ago

Circulating tumor cells • Next-generation sequencing • Tumor cell

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NF2 (Neurofibromin 2) • NOTCH3 (Notch Receptor 3) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)

TP53 mutation • KRAS mutation • BRAF mutation • NF2 mutation • NOTCH3 mutation

Oncomine™ Pan-Cancer Cell-Free Assay • Oncomine™ Comprehensive Assay Plus

1year

Unilateral Multifocal Inner Ear and Internal Auditory Canal or Cerebellopontine Angle Cochleovestibular Schwannomas-Genetic Analysis and Management by Surgical Resection and Cochlear Implantation. (PubMed, Otol Neurotol)

The occurrence of multifocal unilateral cochleovestibular schwannomas without pathogenic variants in NF2 in non-affected blood leucocytes can be associated with mosaic NF2-related schwannomatosis (case 1), or with likely sporadic mutations (case 2) and may be overlooked due to their extreme rarity. Although challenging, successful hearing rehabilitation could be achieved through surgical resection of the tumors and cochlear implantation.

1 year ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation

1year

Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma (clinicaltrials.gov)

P1/2; Completed --> Terminated; Sponsor terminated study agreement

1 year ago

Combination therapy • Trial termination

NF2 (Neurofibromin 2)

NF2 mutation

MSK-IMPACT

cisplatin • pemetrexed • pevonedistat (MLN4924)

1year

Characterizing sarcoma molecular landscape by nanopore adaptive sampling sequencing (Sarcoma-RC 2024)

Sarcoma panel Nanopore adaptive sampling can diagnose rare sarcoma types, such as FUS translocated Ewing's sarcoma, and aid in characterizing the molecular landscape. Furthermore, Nanopore analysis may facilitate blood-based tumor markers. Additional testing of a diverse sarcoma cohort is needed to evaluate the clinical utility of this approach.

1 year ago

NF2 (Neurofibromin 2) • FUS (FUS RNA Binding Protein)

NF2 mutation

FoundationOne® CDx

1year

Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors Enriched for Tumors With NF2 Gene Mutations (clinicaltrials.gov)

P1, N=188, Recruiting, Vivace Therapeutics, Inc | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Nov 2024

1 year ago

Trial completion date • Trial primary completion date • Metastases

NF2 (Neurofibromin 2)

NF2 mutation

VT3989

1year

Tissue genomic profiling of pleural mesothelioma patients treated with immunotherapy: Unraveling genetic alterations and complexity (ELCC 2024)

Conclusions Our study did not identify predictive or prognostic factors for IO outcomes in unresectable PM, emphasizing the complexity and heterogeneity of PM. Further research with larger cohorts is crucial to unveil biomarkers in this setting.

1 year ago

Clinical • Tumor mutational burden • IO biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • FANCA (FA Complementation Group A)

PIK3CA mutation • BAP1 mutation • NF2 mutation • FANCA mutation

FoundationOne® CDx • OmniSeq INSIGHT

1year

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature. (PubMed, Arch Pathol Lab Med)

Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling...One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

1 year ago

Review • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF2 (Neurofibromin 2) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

CDKN2A mutation • NF2 mutation • NF2 negative

sirolimus

1year

Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study. (PubMed, J Neurosurg)

These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.

1 year ago

Clinical • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NF2 (Neurofibromin 2) • KLF4 (Kruppel-like factor 4)

PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • AKT1 E17K • NF2 mutation • AKT1 mutation • PIK3CA E545 • KLF4 K409Q

1year

Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation. (PubMed, Acta Neuropathol)

These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

1 year ago

Journal

NF2 (Neurofibromin 2)

NF2 mutation • NF2 expression

1year

Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance. (PubMed, Nat Commun)

Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2.

1 year ago

Journal

NF1 (Neurofibromin 1) • NF2 (Neurofibromin 2)

NF2 mutation

Koselugo (selumetinib)

1year

SEL-TH-1601: Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors (clinicaltrials.gov)

P2, N=34, Active, not recruiting, Children's Hospital Medical Center, Cincinnati | Recruiting --> Active, not recruiting

1 year ago

Enrollment closed

NF2 (Neurofibromin 2)

NF2 mutation

Koselugo (selumetinib)

1year

POPLAR-NF2: Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas (clinicaltrials.gov)

P2/3, N=89, Recruiting, Recursion Pharmaceuticals Inc.

1 year ago

Trial completion date • Trial primary completion date

NF2 (Neurofibromin 2)

NF2 mutation

REC-2282

1year

Long-term outcomes of stereotactic radiosurgery for intracranial schwannoma in neurofibromatosis type 2: a genetic analysis perspective. (PubMed, J Neurooncol)

SRS achieved excellent PFR for NF2-associated intracranial schwannomas in the mild (group 2A) and moderate (group 2B) groups. SRS necessitates careful consideration for the severe group (group 3), especially in cases with NF2 truncating mutation exons 2-13.

1 year ago

Journal • Surgery

NF2 (Neurofibromin 2)

NF2 mutation