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BIOMARKER:

NF1 deletion

i
Other names: NFNS, NF1, Neurofibromin 1, Neurofibromatosis-Related Protein NF-1, Truncated Neurofibromin 1
Entrez ID:
Related biomarkers:
5ms
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.
Late-breaking abstract
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • NF1 (Neurofibromin 1)
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TP53 mutation • NF1 mutation • H3.3K27M • NF1 deletion
8ms
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.
Observational data • Journal
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NF1 (Neurofibromin 1)
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NF1 deletion
9ms
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.
Clinical • Review • Journal
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NF1 (Neurofibromin 1)
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NF1 deletion
9ms
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.
Preclinical • Journal
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NF1 (Neurofibromin 1) • SH2B3 (SH2B Adaptor Protein 3)
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NF1 mutation • NF1 deletion • SH2B3 deletion
10ms
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.
Clinical • Review • Journal
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NF1 (Neurofibromin 1)
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NF1 mutation • NF1 deletion
10ms
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.
Clinical • Journal • BRCA Biomarker
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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)
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BRCA2 deletion • BRCA1 deletion • NF1 deletion
11ms
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.
Journal
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • 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)
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KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • FGFR2 mutation • KIT mutation • NF1 mutation • CDKN2A mutation • NF1 deletion
11ms
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.
Clinical • Journal
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NF1 (Neurofibromin 1) • NF2 (Neurofibromin 2)
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NF1 deletion
11ms
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.
Journal
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NF1 (Neurofibromin 1)
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NF1 deletion
11ms
[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.
Clinical
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NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • ZFTA (Zinc Finger Translocation Associated)
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NTRK2 fusion • CDKN2A deletion • NF1 deletion
12ms
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.
Journal
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NF1 (Neurofibromin 1)
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NF1 deletion • NF1 rearrangement
1year
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.
Clinical • Journal
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NF1 (Neurofibromin 1) • RHOA (Ras homolog family member A)
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NF1 deletion
1year
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.
Clinical • Journal
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NF1 (Neurofibromin 1)
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NF1 deletion
1year
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.
Clinical • Journal
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BRAF (B-raf proto-oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • SOS1 (SOS Ras/Rac Guanine Nucleotide Exchange Factor 1)
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NF1 deletion
1year
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.
Clinical • Journal
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NF1 (Neurofibromin 1)
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NF1 mutation • NF1 deletion
1year
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.
Journal
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NF1 (Neurofibromin 1)
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NF1 mutation • NF1 deletion
over1year
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.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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NF1 deletion
almost2years
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.
Preclinical • Journal
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NF1 (Neurofibromin 1)
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NF1 mutation • NF1 deletion
almost2years
[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.
Clinical
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CDKN2A (Cyclin-dependent kinase inhibitor 2A) • SOX10 (SRY-Box 10)
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CDKN2A deletion • CDKN2A mutation • NF1 deletion
almost2years
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.
Journal • Tumor-Infiltrating Lymphocyte
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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) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • FOXA1 (Forkhead Box A1)
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TP53 mutation • ER positive • HER-2 amplification • HER-2 mutation • PTEN mutation • ARID1A mutation • NF1 mutation • NF1 deletion • AKT1 mutation • TILs
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MSK-IMPACT
2years
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.
Journal
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TP53 (Tumor protein P53) • DUSP6 (Dual specificity phosphatase 6)
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NF1 deletion • DUSP6 expression
2years
NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas. (PubMed, Cancer Med)
Overall survival and disease-free survival were statistically better in patients with NF1 alterations (N = 34) than in patients with KRAS mutations (N = 30) in univariate analysis. Our results confirm that NF1 is frequently mutated and represents a distinct molecular and clinical subtype of lung adenocarcinoma.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NF1 (Neurofibromin 1)
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KRAS mutation • NF1 mutation • NF1 deletion • EGFR mutation + KRAS mutation
2years
Nf1 deletion results in depletion of the Lhx6 transcription factor and a specific loss of parvalbumin cortical interneurons. (PubMed, Proc Natl Acad Sci U S A)
Moreover, molecular and cellular properties of parvalbumin (PV)-positive CINs were altered by the loss of Nf1, without changes in somatostatin (SST)-positive CINs. We discovered that loss of Nf1 results in a dose-dependent decrease in Lhx6 expression, the transcription factor necessary to establish SST and PV CINs, which was rescued by the MEK inhibitor SL327, revealing a mechanism whereby a neurofibromin/Ras/MEK pathway regulates a critical CIN developmental milestone.
Journal
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NF1 (Neurofibromin 1)
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NF1 mutation • NF1 deletion
over2years
Beyond "Triton": Malignant Peripheral Nerve Sheath Tumors With Complete Heterologous Rhabdomyoblastic Differentiation Mimicking Spindle Cell Rhabdomyosarcoma. (PubMed, Am J Surg Pathol)
MPNST may occasionally show complete heterologous rhabdomyoblastic differentiation without histologic evidence of residual conventional MPNST, closely mimicking spindle cell RMS. IHC for H3K27me3 reliably distinguishes MPNST from spindle cell RMS.
Journal
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TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1) • SOX10 (SRY-Box 10) • APP (Amyloid Beta Precursor Protein)
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TP53 mutation • NF1 mutation • NF1 deletion • CDKN2A mutation + TP53 mutation
over2years
Genetic analyses of mosaic neurofibromatosis type 1 with giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi. (PubMed, J Dermatol)
These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.
Journal
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NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1)
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NF1 mutation • NF1 deletion • NRAS Q61