Neurofibromin: a general outlook

Trovó-Marqui, A.B.; Tajara, EH

doi:10.1111/j.1399-0004.2006.00639.x

Cited by 178 publications

(140 citation statements)

References 138 publications

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“…These deletions involve many genes that were earlier reported to be frequently lost by deletion, mutation or promoter methylation events in various solid tumours and acute leukaemia, such as ETV6 (12p13), SLIT2(4p15), AUTS2(7q11), NF1(17q12), MSH5 (6p21), MSH3(5q), HUS1(7p12), CDKN2D(19p13.2), WISP-1(8q24), IDE or TLX2(2p13.1). 14,[16][17][18][19][20][21][22][23][24] These genes are involved in major cellular processes, including DNA repair (MSH3, MSH5, HUS1), cell cycle regulation (HUS1, CDKN2D) and the RAS pathway (NF1). Another gene, IDE (10q32), a putative tumour suppressor insulin degrading enzyme, may play a role as a RB protector by preventing inactivation of RB1.…”

Section: Discussionmentioning

confidence: 99%

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease

et al. 2009

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neoplasms (HDN) constitute a rare disease characterized by aggressive clinical behaviour and a poor prognosis. Tumour cells from HDN are leukaemic counterparts of plasmacytoid dendritic cells (pDCs). Despite increased knowledge of the ontogenetic origin of these tumours, the genetic causes and oncogenic signalling events involved in malignant transformation are still unknown. To delineate novel candidate regions and disease-related genes, we studied nine typical CD4 þ CD56 þ HDN cases using genome-wide high-resolution array comparative genomic hybridization (CGH). Genomic imbalances, which were predominantly losses, were frequently detected. Gross genomic losses or gains involving an entire chromosome were observed in eight cases. The most frequent imbalances were deletions of chromosome 9, chromosome 13 and partial losses affecting 17p or 12p. Combinations of deletions of tumour suppressor genes (TSG), namely RB1, CDKN1B (p27), CDKN2A, (p16 ink4a , p14 arf ) or TP53 (p53), were observed in all cases. These results indicate that deletion events altering G1/S regulation are crucial for HDN oncogenesis. Furthermore, in addition to frequent sporadic gene losses, in one case we observed a 8q24 interstitial deletion that brought MYC closer to miR-30b/miR30d, which may be related to their deregulation. Taken together, these results indicate that in addition to frequent G1/S checkpoint alterations, various genetic events could contribute to the chemoresistance of the tumour.

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Section: Discussionmentioning

confidence: 99%

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease

et al. 2009

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“…4 Individuals with NF1 microdeletion syndrome have a more severe phenotype than those with NF1 due to intragenic mutations, with the microdeletion syndrome characterized by facial dysmorphisms, developmental delay (DD), intellectual disability (ID), and excessive neurofibromas. 5,6 The NF1 microdeletions are caused by nonallelic homologous recombination (NAHR) between the low-copy repeats (LCRs) that flank this region. 7 The deletions may be 1.0-1.4 Mb in size depending on the specific LCR mediating the deletion and are classified as types 1-3.…”

Section: Introductionmentioning

confidence: 99%

NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype

Moles

Gowans

Gedela

et al. 2012

Genetics in Medicine

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Purpose: Neurofibromatosis, type 1 (NF1) is an autosomal dominant disorder caused by mutations of the neurofibromin 1 (NF1) gene at 17q11.2. Approximately 5% of individuals with NF1 have a 1.4-Mb heterozygous 17q11.2 deletion encompassing NF1, formed through nonallelic homologous recombination (NAHR) between the low-copy repeats that flank this region. NF1 microdeletion syndrome is more severe than NF1 caused by gene mutations, with individuals exhibiting facial dysmorphisms, developmental delay (DD), intellectual disability (ID), and excessive neurofibromas. Although NAHR can also cause reciprocal microduplications, reciprocal NF1 duplications have been previously reported in just one multigenerational family and a second unrelated proband. methods:We analyzed the clinical features in seven individuals with NF1 microduplications, identified among 48,817 probands tested in our laboratory by array-based comparative genomic hybridization. Results:The only clinical features present in more than one individual were variable DD/ID, facial dysmorphisms, and seizures. No neurofibromas were present. Three sets of parents were tested: one duplication was apparently de novo, one inherited from an affected mother, and one inherited from a clinically normal father.conclusion: This is the first report comparing the phenotypes of nonrelated individuals with NF1 microduplications. This comparison will allow for further definition of this emerging microduplication syndrome.Genet Med 2012:14(5):508-514

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“…Different human mutations across the entire NF1 gene have been identified from various studies [15] but a clear correlation between specific mutation and clinical presentations has not been shown. Neurofibromin, in correspondence of exons 20-27a, has a region of homology with p120-GAP that is a GTPase-activing protein (GAP) for the ras family of proto-oncogenes [16]. This 'GAP related domain'(GRD) accelerates the GTP-hydrolysis activity and thus deregulates p21-ras.…”

Section: Genetic and Tumorigenesismentioning

confidence: 99%

The Neurofibromatosis type 1:A dominantly inherited tumors-predisposing disorder

et al. 2009

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AbstractNeurofibromatosis type I (NF1) is a hereditary multisystem disease involving the skin and nervous system. It is the most common form of autosomal dominant phakomatoses with 100% penetrance but wide phenotypic variability. The NF1 gene is located on chromosome 17q11.2 and encodes for a tumour suppressor protein. Because affected individuals have an increased risk of tumor formation, this disorder is classified as inherited cancer syndrome. The risk of malignancies in NF1 affected patients is estimated to be 5–15% higher than in the general population. We reviewed clinical aspects and genetic mechanisms of tumorigenesis in NF1 affected patients.

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Neurofibromin: a general outlook

Cited by 178 publications

References 138 publications

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease

NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype

The Neurofibromatosis type 1:A dominantly inherited tumors-predisposing disorder

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