News - NF1 deletion - LARVOL VERI

ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new. (PubMed, Virchows Arch)

The authors review the sparse literature on molecular-genetic aberrations involving the epidermal growth factor receptor family of receptor tyrosine kinases (ERBB1/EGFR, ERBB2, ERBB3, and ERBB4) in uterine mesenchymal tumors, a review that suggests that such tumors may be pathologically heterogeneous. The potential clinical significance of demonstrating a targetable ERBB2/ERBB3 tyrosine kinase mutation or other EGFR family aberrations, as well as its distinctive pathologic profile, supports the segregation of the tumor reported herein as a distinct and emerging entity.

6 days ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ATRX (ATRX Chromatin Remodeler) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • SOX10 (SRY-Box 10) • CD68 (CD68 Molecule) • MME (Membrane Metalloendopeptidase) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLANA (Melan-A) • NTRK (Neurotrophic receptor tyrosine kinase) • PDGFB (Platelet Derived Growth Factor Subunit B) • STAT6 (Signal transducer and activator of transcription 6) • MITF (Melanocyte Inducing Transcription Factor)

EGFR mutation • HER-2 mutation • CDKN2A deletion • ATRX mutation • ERBB3 mutation • NF1 deletion

3ms

Pigment epithelium derived factor drives melanocyte proliferation and migration in neurofibromatosis café au lait macules. (PubMed, Skin Health Dis)

Melanocyte proliferation and migration leading to CALMs in NF1 arises from biallelic NF1 loss, resulting in RAS/MAPK pathway activation, and reduced expression of the tumour suppressor PEDF. Activation of the PI3K/AKT pathway in classical NF1 and NF1 melanoma may facilitate tumour growth.

3 months ago

Journal

NF1 (Neurofibromin 1) • MITF (Melanocyte Inducing Transcription Factor)

NF1 deletion

7ms

CRISPR-Cas9 library screening combined with an exosome-targeted delivery system addresses tumorigenesis/TMZ resistance in the mesenchymal subtype of glioblastoma. (PubMed, Theranostics)

Each of these subtypes exhibits a varying degree of sensitivity to the temozolomide (TMZ) treatment, while the prognosis corresponds to the molecular and genetic characteristics of the tumor cell type...A quadruple combination therapy based on a targeted Exos delivery system demonstrated significantly reduced tumor burden in vivo. Therefore, our study provides new insights and therapeutic approaches for regulating tumor progression and TMZ resistance in the MES-GBM subtype.

7 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1) • RASGRP1 (RAS Guanyl Releasing Protein 1)

KRAS mutation • KRAS G12C • KRAS G12 • NF1 deletion • KRAS overexpression

temozolomide

9ms

Generation of heterozygous and homozygous NF1 lines from human-induced pluripotent stem cells using CRISPR/Cas9 to investigate bone defects associated with neurofibromatosis type 1. (PubMed, Front Cell Dev Biol)

In addition, we show that a mono-allelic deletion in NF1 in an isogenic context is sufficient to impair cell differentiation into osteoblasts. Overall, this study highlights the relevance of generating isogenic lines, which may help in genotype-phenotype correlation and provide a human cellular model to understand the molecular mechanisms underlying NF1 and, thus, discover new therapeutic strategies.

9 months ago

Journal

NF1 (Neurofibromin 1)

NF1 mutation • NF1 deletion

9ms

Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review. (PubMed, BMC Med Genomics)

In this study, we analysed 22 NF1 deletion patients by genome-wide array-CGH with the aim (1) to correlate deletion length to observed phenotypic features and their severity in NF1 deletion syndrome, and (2) to identify whether the deletion phenotype could also be modulated by copy number variations elsewhere in the genome. We then review the role of co-deleted genes in the 1.4 Mb interval of type-1 deletions, and their possible implication in the main clinical features observed in this high-risk group of NF1 patients.

9 months ago

Review • Journal

NF1 (Neurofibromin 1)

NF1 deletion

12ms

Breast cancer risk in NF1-deleted patients. (PubMed, J Med Genet)

No abstract available

12 months ago

Journal

NF1 (Neurofibromin 1)

NF1 deletion

1year

Droplet digital PCR for fast and accurate characterization of NF1 locus deletions: confirmation of the predominant maternal origin of type-1 deletions. (PubMed, J Mol Diagn)

We propose a fast and efficient ddPCR quantification to allow fine NF1 deletion classification; ddPCR can easily be implemented into routine diagnosis to complement the techniques dedicated to NF1 point variants identification. This new tool may help unravel the genetic basis conditioning phenotypic variability in NF1 deleted patients and offer tailored genetic counselling.

1 year ago

Journal

NF1 (Neurofibromin 1) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

NF1 deletion

1year

A bedside-to-bench translational analysis demonstrates that NF1 alterations promote CDK4/6 inhibitor (CDK4/6i) resistance in hormone receptor-positive (HR+) metastatic breast cancer (MBC) (SABCS 2023)

MCF7 wild-type (WT) and two NF1-knockout (KO) clones were treated with palbociclib Â± estrogen deprivation, followed by cell viability assays... Using multicenter clinical and real-world evidence, we demonstrate that NF1-MUT is associated with inferior duration and worse outcomes on CDK4/6i in MBC. Pts with baseline pNF1-MUT on 1L CDK4/6i and endocrine therapy had a median PFS below typical responses expected in clinical practice. A link between NF1 loss and CDK4/6i resistance was supported by in vitro experiments in HR+ breast cancer cells.

1 year ago

Metastases

HER-2 (Human epidermal growth factor receptor 2) • NF1 (Neurofibromin 1) • CDK4 (Cyclin-dependent kinase 4)

HR positive • HER-2 negative • HER-2 expression • NF1 mutation • NF1 deletion • CDK4 mutation

Guardant360® CDx

Ibrance (palbociclib)

over1year

Genomic heterogeneity of ALK rearrangements and acquired resistance pathways in ALK+ Advanced non-small cell lung cancer (NSCLC) treated with upfront alectinib: Preliminary results of GALILEO project (ESMO 2023)

Legal entity responsible for the study Fondazione Policlinico Universitario A Gemelli â€“ IRCCS. In post-lorlatinib NGS-assay, 2 pts had ALK-compound mutations, while 4 pts had newly off-target alterations (CDKN2A/B CDKN2B loss, NF1 deletion, DNMT3A/ARID1A/CHECK2 M+). Conclusions Implementation of longitudinal genomic assessment is required in order to provide an extensive overview of resistance mechanisms and clinical outcomes according to current ALK-inhibitors treatment sequences.

over 1 year ago

Preclinical • Metastases

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • CDKN2A deletion • ALK G1202R • NF1 deletion • ALK I1171N • ALK I1171 • ALK E1210K • CDKN2B deletion • EML4-ALK G1202R

FoundationOne® CDx • FoundationOne® Liquid CDx

Alecensa (alectinib) • Lorbrena (lorlatinib)

over1year

Deregulated expression of polycomb repressive complex 2 target genes in a NF1 patient with microdeletion generating the RNF135-SUZ12 chimeric gene. (PubMed, Neurogenetics)

These results suggest that RNF135-SUZ12 chimera may acquire a gain of function, compared with SUZ12 wild type in the PRC2 complex, and a loss of function relative to RNF135 wild type. Both events may have a role in the early onset of the patient's neurofibromas.

over 1 year ago

Journal

TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

NF1 mutation • NF1 deletion • TP53 expression

almost2years

Vertical MAPK pathway targeting in novel genetically engineered mouse and cell line models of NF1-altered melanoma: the mSK-Mel murine cohort (AACR 2023)

In syngeneic xenograft models of NF1/TP53/BRAFVE mutation, MEK inhibition alone, or in combination with RAF and/or SHP inhibition, induced tumor regression and delayed the onset of resistance and progression as compared to doublet RAF/SHP inhibitor therapy. Overall, we demonstrated the efficacy and feasibility of vertical MAPK pathway targeting in a novel cohort of genetically relevant mouse and cell line models of NF1-mutant melanoma and provide justification for future studies of vertical MAPK pathway targeting to achieve maximal ERK pathway inhibition in this molecularly defined patient cohort.

almost 2 years ago

Preclinical • IO biomarker

NF1 (Neurofibromin 1)

TP53 mutation • BRAF mutation • NF1 mutation • RAS mutation • NF1 deletion

almost2years

MEK inhibition causes BIM stabilization and increased sensitivity to BCL-2 family member inhibitors in RAS-MAPK-mutated neuroblastoma. (PubMed, Front Oncol)

In vivo combination of trametinib with BCL-2 inhibitors led to tumor inhibition in NRAS-mutant and NF1-deleted xenografts. Together, these results show that combining MEK inhibition with BCL-2 family member inhibition could potentially improve therapeutic outcomes for RAS-MAPK-mutated neuroblastoma patients.

almost 2 years ago

Journal • IO biomarker

NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • NF1 (Neurofibromin 1)

NRAS mutation • RAS mutation • NF1 deletion

Venclexta (venetoclax) • Mekinist (trametinib) • navitoclax (ABT 263)

almost2years

Imagawa-Matsumoto syndrome: SUZ12-related overgrowth disorder. (PubMed, Clin Genet)

We also report on a novel IMMAS patient carrying a splicing variant (c.1023?+?1G?>?C) in SUZ12. This patient had a milder phenotype than other previously reported IMMAS cases, with no macrocephaly or overgrowth phenotypes, highlighting the clinical variation in IMMAS.

almost 2 years ago

Review • Journal

NF1 (Neurofibromin 1) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

NF1 deletion

2years

Identification of a novel NF1 deletion variant in a Taiwanese boy with neurofibromatosis type 1-associated Moyamoya syndrome. (PubMed, Pediatr Neonatol)

No abstract available

2 years ago

Journal

NF1 (Neurofibromin 1)

NF1 deletion

2years

Unmatched Whole-Genome Sequencing As a Clinical Tool for Hematological Neoplasms with Significant Utility in Cases with Tumor-in-Normal Contamination (ASH 2022)

Conclusions We have developed and validated an uWGS workflow for the detection of clinically relevant alterations in leukemia across variant classes to include CNVs, translocations and point mutations. We demonstrated that for hematological neoplasms, uWGS rescues events that can be missed by mWGS workflows owing to TiN, which shows how uWGS enables the detection of clinically relevant biomarkers, and the opportunity to discover new clinical findings using a single test and a single biopsy.

2 years ago

Clinical

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CHEK2 (Checkpoint kinase 2) • JAK1 (Janus Kinase 1) • PAX5 (Paired Box 5) • EP300 (E1A binding protein p300) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • ZEB2 (Zinc Finger E-Box Binding Homeobox 2) • ZNF384 (Zinc Finger Protein 384)

CDKN2A deletion • NF1 deletion • PAX5 mutation

2years

Elucidating the diversity of malignant mesenchymal states in glioblastoma by integrative analysis. (PubMed, Genome Med)

Diverse MES states occur in glioblastoma. These states share a subset of core genes but differ primarily in their association with hypoxia vs. astrocytic expression programs, and with immune suppression vs. activation, respectively.

2 years ago

Journal

NF1 (Neurofibromin 1)

NF1 deletion

almost3years

NF1 deletion potentiates tumorigenesis and activates expression of cancer-related kinases in an iPSC-based model of H3.3K27M diffuse intrinsic pontine glioma (AACR 2022)

Taken together, these data show that NF1 deletion is associated with a significant alteration of kinase expression in H3.3K27M iDIPG, potentially opening up a new therapeutic avenue in these devastating tumors. Further work using this model will focus on screening for kinases necessary for TNK iDIPG neurospheres survival in culture and investigating synergy between targeted kinase inhibition and HDAC inhibitors, which have shown promise in H3.3K27M DIPG.

almost 3 years ago

Late-breaking abstract

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • NF1 (Neurofibromin 1)

TP53 mutation • NF1 mutation • H3.3K27M • NF1 deletion

3years

Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study. (PubMed, Eur J Hum Genet)

Learning difficulties, however, appear to affect a significant proportion of NF1 subjects with this phenotype. Knowledge of this genotype-phenotype association is fundamental to accurate prognostication for families and caregivers.

3 years ago

Observational data • Journal

NF1 (Neurofibromin 1)

NF1 deletion

3years

Classification of NF1 microdeletions and its importance for establishing genotype/phenotype correlations in patients with NF1 microdeletions. (PubMed, Hum Genet)

However, these correlations are critically dependent upon the accurate characterization of the deletions in terms of their extent. In this review, we outline the utility as well as the shortcomings of multiplex ligation-dependent probe amplification (MLPA) to classify the different types of NF1 microdeletion and indicate the importance of high-resolution microarray analysis for correct classification, a necessary precondition to identify those genes responsible for the NF1 microdeletion syndrome.

3 years ago

Clinical • Review • Journal

NF1 (Neurofibromin 1)

NF1 deletion

3years

Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia. (PubMed, Blood Adv)

Deletion of Sh2b3 cooperates with conditional Nf1 deletion in a dose-dependent fashion. These studies illustrate that haploinsufficiency for Sh2b3 contributes to the severity of myeloproliferative disease and provide an experimental system for testing treatments for a high-risk cohort of JMML patients.

3 years ago

Preclinical • Journal

NF1 (Neurofibromin 1) • SH2B3 (SH2B Adaptor Protein 3)

NF1 mutation • NF1 deletion • SH2B3 deletion

3years

Atypical NF1 Microdeletions: Challenges and Opportunities for Genotype/Phenotype Correlations in Patients with Large NF1 Deletions. (PubMed, Genes (Basel))

The atypical NF1 deletion in this patient does not include the SUZ12 gene but does encompass CRLF3. Comparative analysis of such atypical NF1 deletions suggests that SUZ12 hemizygosity is likely to contribute significantly to the reduced cognitive abilities, severe global developmental delay and facial dysmorphisms observed in patients with type 1 NF1 deletions.

3 years ago

Clinical • Review • Journal

NF1 (Neurofibromin 1)

NF1 mutation • NF1 deletion

3years

Discovery of structural deletions in breast cancer predisposition genes using whole genome sequencing data from > 2000 women of African-ancestry. (PubMed, Hum Genet)

Many of the deletions, particularly those resulting in protein truncations, are likely to be pathogenic. Results from this study, if confirmed in future large-scale studies, could have significant implications for genetic testing for this common cancer.

3 years ago

Clinical • Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

BRCA2 deletion • BRCA1 deletion • NF1 deletion

3years

Intragenic NF1 deletions in sinonasal mucosal malignant melanoma. (PubMed, Pigment Cell Melanoma Res)

Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1 mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors.

3 years ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MITF (Melanocyte Inducing Transcription Factor)

KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • KIT mutation • FGFR2 mutation • NF1 mutation • CDKN2A mutation • NF1 deletion

over3years

Analysis of NF1 gene variants among thirteen patients with neurofibromatosis type 1 (PubMed, Zhonghua Yi Xue Yi Chuan Xue Za Zhi)

Variants of the NF1 gene probably underlay the disease among these children. Above findings have enriched the the spectrum of NF1 gene variants.

over 3 years ago

Clinical • Journal

NF1 (Neurofibromin 1) • NF2 (Neurofibromin 2)

NF1 deletion

over3years

Assessment of H3K27me3 immunohistochemistry and combination of NF1 and p16 deletions by fluorescence in situ hybridization in the differential diagnosis of malignant peripheral nerve sheath tumor and its histological mimics. (PubMed, Diagn Pathol)

FISH for NF1 and p16 deletions, frequently observed in high-grade MPNSTs, might be a useful ancillary diagnostic tool for differentiating MPNST from other mimicking spindle cell and pleomorphic sarcomas.

over 3 years ago

Journal

NF1 (Neurofibromin 1)

NF1 deletion

over3years

[VIRTUAL] OPTICAL GENOME MAPPING REVEALS NOVEL STRUCTURAL VARIANTS IN PEDIATRIC BRAIN TUMORS (SIOP 2021)

OGM effectively identifies novel clinically relevant SVs in pediatric brain tumor samples, including SVs that were not discovered other methods of testing. This is a promising new method to map the full SV spectrum of pediatric brain tumors. Future studies will expand testing to a larger cohort of samples to better understand the full spectrum of SVs and begin clinical analysis to determine the effect of SVs on response to treatment/prognosis.

over 3 years ago

Clinical

NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • ZFTA (Zinc Finger Translocation Associated)

NTRK2 fusion • CDKN2A deletion • NF1 deletion

over3years

Unusual split green-orange signals in USP6 fluorescence in situ hybridization in a malignant peripheral nerve sheath tumor with a novel NF1-SCIMP fusion: a potential diagnostic pitfall. (PubMed, Virchows Arch)

To the best of our knowledge, this is the first case with a confirmed NF1 gene fusion partner in a peripheral nerve sheath tumor. Notably, rearrangement of the SCIMP may cause a pitfall in the interpretation of USP6 FISH results.

over 3 years ago

Journal

NF1 (Neurofibromin 1)

NF1 deletion • NF1 rearrangement

over3years

Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microdeletion syndrome establishes CRLF3 as a critical regulator of neurogenesis. (PubMed, Cell Rep)

Furthermore, we demonstrate a higher autistic trait burden in NF1 patients harboring a deleterious germline mutation in the CRLF3 gene (c.1166T>C, p.Leu389Pro). Collectively, these findings identify a causative gene within the NF1-TGD locus responsible for hCO neuronal abnormalities and autism in children with NF1.

over 3 years ago

Clinical • Journal

NF1 (Neurofibromin 1) • RHOA (Ras homolog family member A)

NF1 deletion

over3years

Severe Phenotype in Patients with Large Deletions of NF1. (PubMed, Cancers (Basel))

Comparison with previously described "classic" NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.

over 3 years ago

Clinical • Journal

NF1 (Neurofibromin 1)

NF1 deletion

over3years

Expanding the clinical phenotype of RASopathies in 38 Turkish patients, including the rare LZTR1, RAF1, RIT1 variants, and large deletion in NF1. (PubMed, Am J Med Genet A)

While large NF1 deletions were identified in four Neurofibromatosis-NS patients with intellectual disability, intelligence was normal in one patient with missense variant. In conclusion, this study provided three novel variants in LZTR1 and expanded the clinical phenotype of rare RASopathies.

over 3 years ago

Clinical • Journal

BRAF (B-raf proto-oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • SOS1 (SOS Ras/Rac Guanine Nucleotide Exchange Factor 1)

NF1 deletion

over3years

Genotype-Phenotype Associations in Patients With Type-1, Type-2, and Atypical NF1 Microdeletions. (PubMed, Front Genet)

Large tumor load exhibited more frequently in this type of disorder, therefore better understanding of genotype-phenotype correlations and progress of the disease is essential for individuals suffering from neurofibromatosis to improve the quality of their life. Our study presented additional clinical data related to NF1 microdeletion patients especially for pediatric cases and it contributes to the better understanding of this type of disorder.

over 3 years ago

Clinical • Journal

NF1 (Neurofibromin 1)

NF1 mutation • NF1 deletion

over3years

Deletion of the whole NF1 gene in a three-generation family with neurofibromatosis type 1. (PubMed, Neurol Sci)

Our findings are the first to identify whole NF1 deletion in a three-generation family with autosomal dominant NF1 and broaden the understanding of the genetic spectrum of NF1-associated NF1.

over 3 years ago

Journal

NF1 (Neurofibromin 1)

NF1 mutation • NF1 deletion

4years

MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. (PubMed, Nat Commun)

We also provide proof-of-principle that FDA-approved inhibitors with activity against MEKK2 can ameliorate NF1 skeletal pathology. Thus, MEKK2 functions as a MAP3K in the ERK pathway in osteoblasts, offering a potential new therapeutic strategy for the treatment of NF1.

4 years ago

Journal

MAP2K1 (Mitogen-activated protein kinase kinase 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)

NF1 deletion

4years

Brain-wide structural and functional disruption in mice with oligodendrocyte-specific Nf1 deletion is rescued by inhibition of nitric oxide synthase. (PubMed, Proc Natl Acad Sci U S A)

Furthermore, NOS-specific inhibition rescued both measures. These results suggest that oligodendrocyte defects account for aspects of brain dysfunction in NF1 that can be identified by neuroimaging and ameliorated by NOS inhibition.

4 years ago

Preclinical • Journal

NF1 (Neurofibromin 1)

NF1 mutation • NF1 deletion

4years

[VIRTUAL] Osteoclast-Type Giant Cell-Rich Malignant Peripheral Nerve Sheath Tumor: A Unique Case (CAP 2020)

An extensive literature review did not reveal another similar case of OGC-rich MPNST. Our case describes a distinct morphologic presentation of MPNST in NF1 confirmed by immunohistochemistry and molecular analysis.

4 years ago

Clinical

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SOX10 (SRY-Box 10)

CDKN2A deletion • CDKN2A mutation • NF1 deletion

4years

Characterization of stromal tumor-infiltrating lymphocytes and genomic alterations in metastatic lobular breast cancer. (PubMed, Clin Cancer Res)

ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared to IDC metastases.

4 years ago

Journal • Tumor-infiltrating lymphocyte

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • FOXA1 (Forkhead Box A1)

TP53 mutation • ER positive • HER-2 amplification • HER-2 mutation • PTEN mutation • ARID1A mutation • NF1 mutation • AKT1 mutation • NF1 deletion • CDH1 mutation

MSK-IMPACT

over4years

Targeted inhibition of the dual specificity phosphatases DUSP1 and DUSP6 suppress MPNST growth via JNK. (PubMed, Clin Cancer Res)

Targeting DUSP1 and 6 genetically or with BCI effectively inhibits MPNST cell growth and promotes cell death, in vitro and in xenograft models. The data supports further investigation of DUSP inhibition in MPNST.

over 4 years ago

Journal

TP53 (Tumor protein P53) • DUSP6 (Dual specificity phosphatase 6)

NF1 deletion • DUSP6 expression