The NF1 gene in tumor syndromes and melanoma

Kiuru, Maija; Busam, Klaus J.

doi:10.1038/labinvest.2016.142

Cited by 162 publications

(144 citation statements)

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“…Neurofibromin is a negative regulator of the RAS cellular proliferation pathway (42–45). Several other functions of neurofibromin were also reported, among them positive regulation of adenyl cyclase, regulation of cell adhesion and motility, and suppression of epithelial mesenchymal transition (42–45). The NF1 gene is a classical tumor suppressor gene whose inactivation is responsible for the neurofibromatosis type 1 (NF1) tumor predisposition syndrome ().…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of NF1 are also linked to juvenile myelomonocytic leukemia () and Watson syndrome (). The NF1 syndrome is characterized by the development of multiple neurofibromas, café-au-lait spots, and Lisch nodules (42,45). Patients with NF1 syndrome are at increased risk to develop malignant peripheral nerve sheath tumors, phaeochromocytoma, leukemia, glioma, rhabdomyosarcoma, and breast cancer (42,45).…”

Section: Discussionmentioning

confidence: 99%

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Identification of SETD2-NF1 fusion gene in a pediatric spindle cell tumor with the chromosomal translocation t(3;17)(p21;q12)

et al. 2017

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Spindle cell tumors are clinically heterogeneous but morphologically similar neoplasms. The term refers to the tumor cells' long and slender microscopic appearance. Distinct subgroups of spindle cell tumors are characterized by chromosomal translocations and also fusion genes. Other spindle cell tumors exist that have not yet been found to have characteristic, let alone pathognomonic, genetic or pathogenetic features. Continuous examination of spindle cell tumors is likely to reveal other subgroups that may, in the future, be seen to correspond to meaningful clinical differences and may even be therapeutically decisive. We analyzed genetically a pediatric spindle cell tumor. Karyotyping showed the tumor cells to carry a t(3;17)(p21;q12) chromosomal translocation whereas RNA sequencing identified a SETD2-NF1 fusion gene caused by the translocation. RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript. Interphase FISH analysis confirmed the existence of the chimeric gene and showed that there was no reciprocal fusion. The fusion transcript codes for a protein in which the last 114 amino acids of SETD2, i.e., the entire Set2 Rpb1 interacting (SRI) domain of SETD2, are replaced by 30 amino acids encoded by the NF1 sequence. The result would be similar to that seen with truncating SETD2 mutations in leukemias. Absence of the SRI domain would result in inability to recruit SETD2 to its target gene locus through binding to the phosphor-C-terminal repeat domain of elongating RNA polymerase II and may affect H3K36 methylation. Alternatively, loss of one of two functional SETD2 alleles might be the crucial tumorigenic factor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of SETD2-NF1 fusion gene in a pediatric spindle cell tumor with the chromosomal translocation t(3;17)(p21;q12)

et al. 2017

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“…Although coming last in the percentage of cases within melanoma patients with NF1-mutated subtype seems to have a higher mutational burden and strongest UV mutation signature than any of the previous ones [13]. NF1 mutant melanomas -characterised by a high level of CRAF expression and a differential MAPK activation- [14] Another strategy is enhancing the natural cell defences by upregulating key tumour suppressors in melanoma such as p53, phosphatase and tensin homolog (PTEN), and p14-ARF. There is compelling evidence that the physiological regulation of p53 function depends on MDM2 -itself the product of a p53-inducible gene.…”

Section: Melanoma: Physiopathological and Molecular Aspectsmentioning

confidence: 99%

Natural Cytotoxic Diterpenoids, a Potential Source of Drug Leads for Melanoma Therapy

Prieto

Silveira

2019

CPD

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Diterpenes present complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. Phorbol esters have been known for their activity against skin malignancies since ancient times. Taxol was first studied in melanoma cells, and recently ingenol mebutate has been approved for the chemoprevention of melanoma in actinic keratosis patients. Therefore, there is scope for research on this class of compounds. We here aim to review the relevant original research reporting on isolated diterpenes with cytotoxic and/or antitumoral activities upon melanoma cells. By collating and discussing the implications of past and current developments on diterpenes, we hope to steer further interest on this field and facilitate the drug discovery activities of the scientific community towards finding potential alternatives to current melanoma chemotherapy.

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“…Contudo, a mutação do gene NF1 é frequentemente descrita nesta neoplasia, particularmente no melanoma desmoplásico. 35 …”

Section: Revista Spdv 75(1) 2017; Manifestações Cutâneas Das Rasopatiunclassified

Manifestações Cutâneas das Rasopatias

Sousa

Fonseca

Cordeiro

et al. 2017

SPDV

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INTRODUÇÃOOs genes da família RAS codificam uma família de proteí-nas essenciais nas vias de sinalização intracelular e que regulam funções como a sobrevivência, proliferação, diferenciação e senescência celulares.1 Um grupo heterogéneo de doenças genéticas denominadas rasopatias apresentam mutações na linha germinativa dos genes que codificam proteínas da via de sinalização RAS/MAPK.2 Estas doenças têm espetros clínicos distintos mas sobreponíveis nalguns aspetos, predispondo ao desenvolvimento de neoplasias e alterações da mielopoiese na infância. 3O reconhecimento do fenótipo permite o diagnóstico clí-nico das rasopatias, sendo que este pode ser confirmado na maioria dos casos, pelo recurso a estudos genéticos e moleculares. O tratamento das rasopatias é orientado para o controlo dos sintomas, com um seguimento clínico periódico que visa o diagnóstico precoce das complicações associadas, nomeadamente das doenças cardiovasculares e neoplasias. A VIA DE SINALIZAÇÃO RAS/MAPKOs genes da via RAS (Rat Sarcoma) são responsáveis pelas Revista SPDV 75(1) 2017; Manifestações cutâneas das rasopatias; Virgínia Coelho de Sousa, Inês Marques Fonseca, Ana Cordeiro, Maria João Paiva Lopes. Manifestações Cutâneas das Rasopatias

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The NF1 gene in tumor syndromes and melanoma

Cited by 162 publications

References 111 publications

Identification of SETD2-NF1 fusion gene in a pediatric spindle cell tumor with the chromosomal translocation t(3;17)(p21;q12)

Identification of SETD2-NF1 fusion gene in a pediatric spindle cell tumor with the chromosomal translocation t(3;17)(p21;q12)

Natural Cytotoxic Diterpenoids, a Potential Source of Drug Leads for Melanoma Therapy

Manifestações Cutâneas das Rasopatias

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