Array CGH of cutaneous neurofibromas (cNFs) from NF1 patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58000 | GEO | 2014/05/28
SECONDARY ACCESSION(S): PRJNA248674
REPOSITORIES: GEO
Similar Datasets
Project description:Somatic copy number changes in cNFs samples in NF1 patients 9 cNFs and matched DNA samples were hybridised to the SurePrint G3 human 400k CGH microarray
2014-05-28 | E-GEOD-58000 | biostudies-arrayexpress
Project description:Patients carrying an inactive NF1 allele develop tumours of Schwann cell origin called neurofibromas (NFs). Genetically engineered mouse models have significantly enriched our understanding of plexiform forms of NFs (pNFs). However, this has not been the case for cutaneous neurofibromas (cNFs), observed in all NF1 patients, as no previous model recapitulates their development. Here, we show that conditional Nf1 inactivation in Prss56-positive boundary cap cells leads to bona fide pNFs and cNFs. This work identifies subepidermal glia as a likely candidate for the cellular origin of cNFs, and provides insights on disease mechanisms, revealing a long, multistep pathological process in which inflammation play pivotal role. This new mouse model is an important asset for future clinical and therapeutic investigations of NF1-associated neurofibromas.
2020-03-10 | GSE117781 | GEO
Project description:To allow accute charaterization of NF1 locus constitutional microdeletion in 70 NF1 patients, a custom array CGH was developped. Goal was to obtain genomic rearrangements fine characterization in order to perform genotype-phenotype correlation in NF1 microdeleted patients. To serve as a reference group in our genotype-phenotype correlation study in NF1 microdeletion patients, non-deleted NF1 patients (i.e. patients with an intragenic NF1 mutation) were also selected from our database. A total of 389 NF1 patients were included in the reference group of non-deleted patients. Multiple logistic regression was performed to test the association of each clinical feature individually with the type of constitutional NF1 mutation (intragenic mutation vs. microdeletion). The phenotypic traits of the 389 reference patients are available in the "GSE19730_control_patient_characteristics.txt" supplementary file on the Series record.
2010-05-26 | GSE19730 | GEO
Project description:To allow accute charaterization of NF1 locus constitutional microdeletion in 70 NF1 patients, a custom array CGH was developped. Goal was to obtain genomic rearrangements fine characterization in order to perform genotype-phenotype correlation in NF1 microdeleted patients. To serve as a reference group in our genotype-phenotype correlation study in NF1 microdeletion patients, non-deleted NF1 patients (i.e. patients with an intragenic NF1 mutation) were also selected from our database. A total of 389 NF1 patients were included in the reference group of non-deleted patients. Multiple logistic regression was performed to test the association of each clinical feature individually with the type of constitutional NF1 mutation (intragenic mutation vs. microdeletion). The phenotypic traits of the 389 reference patients are available in the "GSE19730_control_patient_characteristics.txt" supplementary file on the Series record. NF1 locus microdeletions characterization vs reference sample (pool of six normal control DNAs)
2010-05-26 | E-GEOD-19730 | biostudies-arrayexpress
Project description:22 plexiform neurofibromas from 18 unrelated neurofibromatosis-type 1 patients were screened with a high resolution array-CGH. Each PNF DNA (somatic tumor DNA) was individually hybridized on Agilent whole human genome 244K microarrays (Platform GPL4091) using the matched genomic constitutional DNA (lymphocytes DNA) from the corresponding patient as reference, in order to detect tumor-specific aberrations. NF1-associated plexiform neurofibromas DNA vs. constitutional DNA
2011-09-29 | E-GEOD-24328 | biostudies-arrayexpress
Project description:Neurofibromatosis type-1 (NF1), caused by heterozygous inactivation of the NF1 tumour suppressor gene, is associated with the development of benign and malignant peripheral nerve sheath tumours (MPNSTs). Although numerous germline NF1 mutations have been identified, relatively few somatic NF1 mutations have been described in neurofibromas. Here we have screened 109 cutaneous neurofibromas, excised from 46 unrelated NF1 patients, for somatic NF1 mutations. NF1 mutation screening (involving loss-of-heterozygosity (LOH) analysis, multiplex ligation-dependent probe amplification and DNA sequencing) identified 77 somatic NF1 point mutations, of which 53 were novel. LOH spanning the NF1 gene region was evident in 25 neurofibromas, but in contrast to previous data from MPNSTs, it was absent at the TP53, CDKN2A and RB1 gene loci. Analysis of DNA/RNA from neurofibroma-derived Schwann cell cultures revealed NF1 mutations in four tumours whose presence had been overlooked in the tumour DNA. Bioinformatics analysis suggested that four of seven novel somatic NF1 missense mutations (p.A330T, p.Q519P, p.A776T, p.S1463F) could be of functional/clinical significance. Functional analysis confirmed this prediction for p.S1463F, located within the GTPase-activating protein-related domain, as this mutation resulted in a 150-fold increase in activated GTP-bound Ras. Comparison of the relative frequencies of the different types of somatic NF1 mutation observed with those of their previously reported germline counterparts revealed significant (P=0.001) differences. Although non-identical somatic mutations involving either the same or adjacent nucleotides were identified in three pairs of tumours from the same patients (P<0.0002), no association was noted between the type of germline and somatic NF1 lesion within the same individual.
| S-EPMC3306856 | biostudies-literature
Project description:Comparison of copy number changes in MPNST samples against benign neurofibromas in NF1 patients
2009-05-20 | GSE16041 | GEO
Project description:<p>Neurofibromatosis type 1 (NF1) is a common tumor-predisposition disorder due to germline mutations in the tumor suppressor gene <i>NF1</i>. A virtually pathognomonic finding of NF1 is the plexiform neurofibroma (PN), a benign, likely congenital tumor that arises from biallelic inactivation of <i>NF1</i>. PN can undergo transformation to a malignant peripheral nerve sheath tumor, an aggressive soft-tissue sarcoma. To better understand the non-<i>NF1</i> genetic contributions to PN pathogenesis, we performed whole-exome sequencing and genome-wide copy-number determination for 23 low-passage Schwann cell cultures established from surgical PN material with matching germline DNA. All resected tumors were derived from routine debulking surgeries. None of the tumors were considered at risk for malignant transformation at the time, <i>e.g.</i>, there was no pain or rapid growth. Deep (~500X) <i>NF1</i> exon sequencing was also conducted on tumor DNA. Non-<i>NF1</i> somatic mutation verification was performed using the Ampliseq/IonTorrent platform. We identified 100% of the germline <i>NF1</i> mutations and found somatic <i>NF1</i> inactivation in 74% of the PN. One individual with three PNs had different <i>NF1</i> somatic mutations in each tumor. The median number of somatic mutations per sample, including <i>NF1</i>, was one (range 0 - 8). <i>NF1</i> was the only gene that was recurrently somatically inactivated in multiple tumors. We found no recurrent non-<i>NF1</i> locus copy-number variation in PN. This is the first multi-sample whole-exome sequencing study of <i>NF1</i>-associated PN. Taken together with concurrent copy-number data, our comprehensive genetic analysis reveals the primacy of <i>NF1</i> loss as the driver of PN tumorigenesis.</p>
| phs001403 | dbGaP
Project description:Neurofibromatosis type 1 (NF1) (MIM#162200) is a relatively frequent genetic condition that predisposes to tumor formation. The main types of tumors occurring in NF1 patients are cutaneous and subcutaneous neurofibromas, plexiform neurofibromas, optic pathway gliomas, and malignant peripheral nerve sheath tumors. To search for somatic mutations in cutaneous (dermal) neurofibromas, whole-exome sequencing (WES) was performed on seven spatially separated tumors and two reference tissues (blood and unaffected skin) from a single NF1 patient. Validation of WES findings was done using routine Sanger sequencing or Sequenom IPlex SNP genotyping. Exome sequencing confirmed the existence of a known familial splice-site mutation NM_000267.3:c.3113+1G>A in exon 23 of NF1 gene (HGMD ID CS951480) in blood, unaffected skin, and all tumor samples. In five out of seven analyzed tumors, we additionally detected second-hit mutations in the NF1 gene. Four of them were novel and one was previously observed. Each mutation was distinct, demonstrating the independent origin of each tumor. Only in two of seven tumors we detected an additional somatic mutation that was not associated with NF1. Our study demonstrated that somatic mutations of NF1 are likely the main drivers of cutaneous tumor formation. The study provides evidence for the rareness of single base pair level alterations in the exomes of benign NF1 cutaneous tumors.
| S-EPMC4795057 | biostudies-literature
Project description:Array data was used to confirm somatic deletion or copy neutral LOH on chromosome 17, that was inclusive of the NF1 gene.
2017-02-21 | GSE95085 | GEO