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)

Partial and complete genome duplications occurred during evolution and resulted in the creation of new genes and gene families. We identified a novel and intricate human gene family located primarily in regions of segmental duplications on human chromosome 1. We named it NBPF, for neuroblastoma breakpoint family, because one of its members is disrupted by a chromosomal translocation in a neuroblastoma patient. The NBPF genes have a repetitive structure with high intragenic and intergenic sequence similarity in both coding and noncoding regions. These similarities might expose these genomic regions to illegitimate recombination, resulting in structural variation in the NBPF genes. The encoded proteins contain a highly conserved domain of unknown function, which we have named the NBPF repeat. In silico analysis combined with the isolation of multiple full-length cDNA clones showed that several members of this gene family are abundantly expressed in a large variety of tissues and cell lines. Strikingly, no discernable orthologues could be identified in the completed genomes of fruit fly, nematode, mouse, or rat, but sequences with low homology could be isolated from the draft canine and bovine genomes. Interestingly, this gene family shows primate-specific duplications that result in species-specific arrays of NBPF homologous sequences. Overall, this novel NBPF family reflects the continuous evolution of primate genomes that resulted in large physiological differences, and its potential role in this process is discussed.
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PMID:A novel gene family NBPF: intricate structure generated by gene duplications during primate evolution. 1607 50

The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17)(p36.2;q11.2) may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types.
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PMID:A constitutional translocation t(1;17)(p36.2;q11.2) in a neuroblastoma patient disrupts the human NBPF1 and ACCN1 genes. 1849 81

Most new genes arise through the duplication of existing genes. In most cases, the duplication is not limited to the coding sequence but encompasses the regulatory region as well. The NBPF gene family has expanded during recent primate evolution, and it has no known mouse ortholog. One of its members, NBPF1, was found to be disrupted by a constitutional translocation in a neuroblastoma patient. Here, we show that the ancestral NBPF gene copied the regulatory region from an unrelated gene, EVI5, after the split between simians and prosimians but before simian radiation. Phylogenetic analysis points to the possible involvement of positive selection acting on the NBPF1 promoter in the simian lineage. We previously showed decreased NBPF1 expression in certain neuroblastoma cell lines. Here, we show that this expression pattern is mimicked by the EVI5 gene, but partly by different mechanisms. Epigenetic regulation of the EVI5 promoter is common in neuroblastoma cell lines, but it is not for the NBPF promoters. Here, we describe the recent acquisition of the NBPF1 promoter from an unrelated gene, and remarkably, both the donor (EVI5) and acceptor (NBPF1) genes are disrupted by constitutional translocations in patients with neuroblastoma, suggesting a functional link between these genes and the disease.
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PMID:The NBPF1 promoter has been recruited from the unrelated EVI5 gene before simian radiation. 1928 12

We are jointly proposing a new name for a protein domain of approximately 65 amino acids that has been previously termed NBPF or DUF1220. Our two labs independently reported the initial studies of this domain, which is encoded almost entirely within a single gene family. The name Neuroblastoma Breakpoint Family ( NBPF) was applied to this gene family when the first identified member of the family was found to be interrupted in an individual with neuroblastoma. Prior to this discovery, the PFAM database had termed the domain DUF1220, denoting it as one of many protein domains of unknown function. It has been PFAM's intention to use "DUF" nomenclature to serve only as a temporary placeholder until more appropriate names are proposed based on research findings. We believe that additional studies of this domain, primarily from our laboratories over the past 10 years, have resulted in furthering our understanding of these sequences to the point where proposing a new name for this domain is warranted. Because of considerable data linking the domain to human-specific evolution, brain expansion and cognition, we believe a name reflecting these findings would be appropriate. With this in mind, we have chosen to name the domain (and the repeat that encodes it) Olduvai. The gene family will remain as NBPF for now. The primary domain subtypes will retain their previously assigned names (e.g. CON1-3; HLS1-3), and the three-domain block that expanded dramatically in the human lineage will be termed the Olduvai triplet. The new name refers to Olduvai Gorge, which is a site in East Africa that has been the source of major anthropological discoveries in the early-mid 1900's. We also chose the name as a tribute to the scientists who made important contributions to the early studies of human origins and our African genesis.
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PMID:A proposal to change the name of the NBPF/DUF1220 domain to the Olduvai domain. 2939 25

We are jointly proposing a new name for a protein domain of approximately 65 amino acids that has been previously termed NBPF or DUF1220. Our two labs independently reported the initial studies of this domain, which is encoded almost entirely within a single gene family. The name Neuroblastoma Breakpoint Family ( NBPF) was applied to this gene family when the first identified member of the family was found to be interrupted in an individual with neuroblastoma. Prior to this discovery, the Pfam database had termed the domain DUF1220, denoting it as one of many protein domains of unknown function. It has been Pfam's intention to use "DUF" nomenclature to serve only as a temporary placeholder until more appropriate names are proposed based on research findings. We believe that additional studies of this domain, primarily from our laboratories over the past 10 years, have resulted in furthering our understanding of these sequences to the point where proposing a new name for this domain is warranted. Because of considerable data linking the domain to human-specific evolution, brain expansion and cognition, we believe a name reflecting these findings would be appropriate. With this in mind, we have chosen to name the domain (and the repeat that encodes it) Olduvai. The gene family will remain as NBPF for now. The primary domain subtypes will retain their previously assigned names (e.g. CON1-3; HLS1-3), and the three-domain block that expanded dramatically in the human lineage will be termed the Olduvai triplet. The new name refers to Olduvai Gorge, which is a site in East Africa that has been the source of major anthropological discoveries in the early-mid 1900's. We also chose the name as a tribute to the scientists who made important contributions to the early studies of human origins and our African genesis.
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PMID:Changing the name of the NBPF/DUF1220 domain to the Olduvai domain. 0