Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Costello syndrome (CS) is a rare congenital anomaly syndrome. Although it may be classified as an "overgrowth" syndrome due to slightly increased birth weight and relative macrocephaly, it is characterized by severe postnatal failure to thrive and short stature. Patients with CS have an increased risk for malignant tumors, a hallmark of several model overgrowth syndromes. The most common tumor in CS is rhabdomyosarcoma (RMS), followed by neuroblastoma and bladder carcinoma. The occurrence of bladder carcinoma in adolescents is distinctly unusual as this is typically a neoplasm of older adults and is not seen with increased frequency in other tumor predisposition syndromes. The increased tumor frequency in CS led to the proposal of a screening protocol, consisting of abdominal and pelvic ultrasounds, and urine studies for catecholamine metabolites and hematuria. It has since become apparent that patients with CS have an increased excretion of catecholamine metabolites in urine without the presence of an identifiable catecholamine secreting tumor. Thus, the urine assay for catecholamines is unhelpful as a screening test for neuroblastoma and should not be used in this population. The benefit of abdominal and pelvic ultrasound and urinalysis for hematuria as screening tests remains to be shown. A timely diagnosis of CS is a necessary prerequisite for awareness of the increased tumor risk. Once a malignancy has been identified, treatment should follow standard protocols. Additional medical problems characteristic for CS, such as hypertrophic cardiomyopathy and arrhythmia, need to be considered and addressed appropriately.
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PMID:Tumor predisposition in Costello syndrome. 1601 Jun 79

Sotos syndrome is an autosomal dominant condition characterized by overgrowth resulting in tall stature and macrocephaly, together with an increased risk of tumorigenesis. The disease is caused by loss-of-function mutations and deletions of the nuclear receptor SET domain containing protein-1 (NSD1) gene, which encodes a histone methyltransferase involved in chromatin regulation. However, despite its causal role in Sotos syndrome and the typical accelerated growth of these patients, little is known about the putative contribution of NSD1 to human sporadic malignancies. Here, we report that NSD1 function is abrogated in human neuroblastoma and glioma cells by transcriptional silencing associated with CpG island-promoter hypermethylation. We also demonstrate that the epigenetic inactivation of NSD1 in transformed cells leads to the specifically diminished methylation of the histone lysine residues H4-K20 and H3-K36. The described phenotype is also observed in Sotos syndrome patients with NSD1 genetic disruption. Expression microarray data from NSD1-depleted cells, followed by ChIP analysis, revealed that the oncogene MEIS1 is one of the main NSD1 targets in neuroblastoma. Furthermore, we show that the restoration of NSD1 expression induces tumor suppressor-like features, such as reduced colony formation density and inhibition of cellular growth. Screening a large collection of different tumor types revealed that NSD1 CpG island hypermethylation was a common event in neuroblastomas and gliomas. Most importantly, NSD1 hypermethylation was a predictor of poor outcome in high-risk neuroblastoma. These findings highlight the importance of NSD1 epigenetic inactivation in neuroblastoma and glioma that leads to a disrupted histone methylation landscape and might have a translational value as a prognostic marker.
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PMID:Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. 2001 18

Although 19p13.13 microdeletion syndrome has been consistently associated with intellectual disability, overgrowth, and macrocephaly, the underlying mechanisms remain unclear. MAST1, a member of the microtubule-associated serine/threonine kinase family, has been suggested as a potential candidate gene responsible for neurologic abnormalities in 19p13.13 microdeletion syndrome, but its role in nervous system development remains to be elucidated. Here, we investigated how MAST1 contributes to neuronal development. We report that MAST1 is upregulated during neuronal differentiation of the human neuroblastoma cell line, SH-SY5Y. Inhibition of MAST1 expression by RNA interference attenuated neuronal differentiation of SH-SY5Y cells. Cell cycle analyses revealed that MAST1-depleted cells did not undergo cell cycle arrest after RA treatment. Consistent with this observation, the number of EdU-positive cells significantly increased in MAST1 knockdown cells. Intriguingly, levels of P27, a cyclin-dependent kinase inhibitor, were also increased during neuronal differentiation, and MAST1 knockdown reduced the expression of P27. Moreover, reduced neuronal differentiation caused by MAST1 depletion was rescued partially by P27 overexpression in SH-SY5Y cells. Collectively, these results suggest that MAST1 influences nervous system development by affecting neuronal differentiation through P27.
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PMID:MAST1 modulates neuronal differentiation and cell cycle exit via P27 in neuroblastoma cells. 3229 63