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

Tumor suppressor genes of neuroblastoma are located at human chromosome 1p36, 4p16, 11q23.3, and 14q32. We have previously cloned and characterized MFRP and RNF26 genes at 11q23.3. Here, we searched for genes within the 1p36.31-p36.23 commonly deleted region between microsatellite markers D1S2731 and D1S2666 by using bioinformatics. D1S2731 was located within FLJ10737 gene, consisting of 16 exons. D1S2666 was located within CAMTA1 gene, consisting of 23 exons. FLJ10737 and CAMTA1 genes were located in the head-to-head manner with an interval of about 83 kb. Exons 1-10 of FLJ10737 gene as well as exons 1-5 of CAMTA1 gene were located within the 1p36.31-p36.23 commonly deleted region. FLJ10737 (559 aa) was found to consist of the DnaJ domain, bipartite nuclear localization signal (NLS), FADH domain, and FEMCA domain. Mouse E030019A03, zebrafish MGC55845, Drosophila CG8531 and Arabidopsis At2g35720 were homologs of human FLJ10737. FADH domain was conserved among vertebrate FLJ10737 orthologs as well as human AD-015, mouse Histocompatibility 47, and rat Ratsg2. KIAA0833 was the representative human CAMTA1 cDNA. Nucleotide sequence of mouse Camta1 cDNA was determined in silico by assembling nucleotide sequences of BY733411, BU610694 ESTs and AK122383 cDNA. Human CAMTA1 (1673 aa) and mouse Camta1 (1682 aa) showed 94.1% total-amino-acid identity. CAMTA1 was a Calmodulin-binding transcription activator (CAMTA) family protein, consisting of CG-1 domain, TIG domain, ankyrin repeats, and IQ motifs. FLJ10737 and CAMTA1 genes on 1p36.31-p36.23 are candidate tumor suppressor genes of neuroblastoma.
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PMID:Identification and characterization of FLJ10737 and CAMTA1 genes on the commonly deleted region of neuroblastoma at human chromosome 1p36.31-p36.23. 1296 7

Deletion of a distal portion of 1p is seen in a wide range of human malignancies, including neuroblastoma. Here, a 1p36.3 commonly deleted region of 216 kb has been defined encompassing two genes, CAMTA1 and FLJ10737. Low expression of CAMTA1 has been recently shown to be an independent predictor of poor outcome in neuroblastoma patients. The present study surveys CAMTA1 and FLJ10737 for genetic alterations by fluorescence-based single strand conformation polymorphism (SSCP) using a panel of DNAs from 88 neuroblastomas, their matching blood samples and 97 unaffected individuals. Nucleotide variants encoding amino acid substitutions were found in both genes. One CAMTA1 variant (T1336I) was not detected in 97 unaffected individuals, another (N1177K) resides in a conserved domain of the CAMTA1 protein and was found hemizygous in six neuroblastomas. We found no evidence for somatic mutations in FLJ10737 or CAMTA1. Further investigations are needed to address the functional impact of the identified variants and their possible significance for neuroblastoma.
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PMID:Allelic variants of CAMTA1 and FLJ10737 within a commonly deleted region at 1p36 in neuroblastoma. 1722 47

Neuroblastomas are characterized by 1p deletions, suggesting that a tumor suppressor gene (TSG) resides in this region. We have mapped the smallest region of deletion (SRD) to a 2 Mb region of 1p36.31 using microsatellite and single nucleotide polymorphisms. We have identified 23 genes in this region, and we have analysed these genes for mutations and RNA expression patterns to identify candidate TSGs. We sequenced the coding exons of these genes in 30 neuroblastoma cell lines. Although rare mutations were found in 10 of the 23 genes, none showed a pattern of genetic change consistent with homozygous inactivation. We examined the expression of these 23 genes in 20 neuroblastoma cell lines, and most showed readily detectable expression, and no correlation with 1p deletion. However, 7 genes showed uniformly low expression in the lines, and 2 genes (CHD5, RNF207) had virtually absent expression, consistent with the expected pattern for a TSG. Our mutation and expression analysis in neuroblastoma cell lines, combined with expression analysis in normal tissues, putative function and prior implication in neuroblastoma pathogenesis, suggests that the most promising TSG deleted from the 1p36 SRD is CHD5, but TNFRSF25, CAMTA1 and AJAP1 are also viable candidates.
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PMID:Expression and sequence analysis of candidates for the 1p36.31 tumor suppressor gene deleted in neuroblastomas. 1766 43

Monosomy 1p36 is one of the most frequent subtelomeric microdeletion syndromes characterized by distinct craniofacial features and developmental delay/mental retardation. Other common symptoms include hypotonia, seizures, brain abnormalities, visual, auditory and heart defects. Neuroblastoma is a rare feature since to our knowledge only two patients with "pure" 1p36 deletion have been described. We report on a child with developmental delay and facial dysmorphy who developed neuroblastoma at 1 month of age. No primary site outside of the liver could be demonstrated and the tumour regressed spontaneously. Standard karyotyping was normal while subtelomeric screening using Multiplex Ligation-dependent Probe Amplification (MLPA) method revealed a constitutional de novo subtelomeric 1p36 deletion. Subsequent Agilent 244K oligonucleotide array-based comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) analysis showed a complex 1p36.3 deletion/duplication rearrangement. Among the best candidate genes predisposing to the development of neuroblastoma located in 1p36, the AJAP1 gene is the only gene present in the duplication while CHD5, TNFRSF25 and CAMTA1 are located outside of the rearrangement. Therefore, a gene-dosage effect involving a gene located in the duplication including AJAP1 might explain the neuroblastoma observed in our patient. The rearrangement might equally interfere with the expression of a gene located outside of it (including CHD5 located 1Mb away from the rearrangement) playing a role in the tumorigenesis. In conclusion, this study illustrates the complexity of such rearrangement characterized by array CGH and strengthens that constitutional 1p36.3 rearrangement predisposes to the development of neuroblastoma.
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PMID:Complex constitutional subtelomeric 1p36.3 deletion/duplication in a mentally retarded child with neonatal neuroblastoma. 1867 3