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)

p58cdc2L1, a protein kinase implicated in apoptotic signaling, is one of eight separate kinases encoded by three tandemly duplicated and linked genes, which we have termed PITSLRE A, B and C. One allele of this complex on chromosome 1 was either deleted or translocated in each of 18 neuroblastoma cell lines with cytogenetically apparent 1p alterations. A protein encoded by this locus, PITSLRE gamma 1, was absent in three of the lines and a smaller, apparently truncated, PITSLRE polypeptide was found in another line. These findings identify a novel gene complex on chromosome 1 that encodes a protein kinase subfamily. We suggest that the PITSLRE locus may harbour one or more tumour suppressor genes affected by chromosome 1p36 modifications in neuroblastoma.
 ...
PMID:Alterations in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma. 792 Jun 54

Childhood endodermal sinus tumors (CESTs) are a unique category of germ cell tumors involving the testis and extragonadal region in children less than 4 years of age. Recent studies of CEST have shown recurrent cytogenetic abnormalities involving the short arm of chromosome 1, most commonly, a deletion of distal 1p. Experience with neuroblastomas has shown that cytogenetic analyses may underestimate the frequency of 1p deletion. To determine the frequency of deletion of Ip in CEST and to verify that 1p is, in fact, deleted and not translocated, we analyzed ten tumors by two-color fluorescence in situ hybridization on single-cell suspensions of interphase nuclei by using a cosmid probe from the PITSLRE kinase (p58) locus (previously mapped to 1p36) cohybridized with plasmid probe pUC1.77 (which recognizes the 1q heterochromatic region) to determine the copy number of chromosome 1. Eight of the ten tumors examined showed evidence of deletion of 1p36. Five of the eight tumors exhibited multiple subdones, and all subdones showed deletion of at least one copy of 1p36, indicating that the deletion probably occurred before the development of chromosome 1 aneusomy. We conclude that deletions of the short arm of chromosome 1, specifically 1p36, do occur in CEST and probably occur at a, higher incidence than that found in neuroblastoma Further studies are needed to determine the degree of overlap of the common area of deletion in CEST with that of neuroblastoma and to determine whether 1p deletion in CEST has prognostic significance.
 ...
PMID:Deletion of 1p36 in childhood endodermal sinus tumors by two-color fluorescence in situ hybridization: a pediatric oncology group study. 916 92

A family of p34Cdc2 related protein kinases, the PITSLRE kinases, is generated by alternative splicing and promoter utilization from three duplicated and tandemly linked genes on human chromosome 1p36.3, which is frequently deleted during the late stages of tumorigenesis. PITSLRE mRNA, protein, and enzyme activity are induced during Fas receptor- and glucocorticoid-mediated apoptosis of human T cells. Several PITSLRE isoforms are specific targets of proteolysis during apoptosis, generating an enzymatically active 50 kDa isoform. Inhibition of this protease activity blocks PITSLRE processing and enzyme activation, as well as apoptosis. Thus, PITSLRE kinases may be integral downstream components of apoptotic signal transduction pathway(s). Furthermore, PITSLRE genes, and their products, are physically altered in human neuroblastoma tumors, suggesting that they may be tumor suppressors.
 ...
PMID:The PITSLRE protein kinase family. 955 75

The family of PITSLRE kinase genes, located in chromosome 1p36, has recently been associated with neuroblastoma tumorigenesis. In order to evaluate the role of these genes as putative tumor suppressor genes, we have analyzed the integrity of the coding region in primary tumors and its location relative to a neuroblastoma consensus deletion. A subset of aggressive neuroblastoma tumors with allelic loss of different parts of chromosome 1p were investigated. Single-strand conformation polymorphism (SSCP), heteroduplex (HD) and sequencing analysis of tumor DNA did not reveal any significant changes in the coding region. In particular, a primary tumor with an interstitial allelic deletion in 1p36 did not reveal concomitant loss of heterozygosity of the PITSLRE gene region when analyzed with a C/T DNA sequence polymorphism in exon 5 of PITSLRE1. FISH analysis on neuroblastoma cell lines with small interstitial deletions and with a balanced translocation in 1p36 revealed that the PITSLRE gene cluster was localized distal to the neuroblastoma consensus deletion. against an involvement of the PITSLRE genes in neuroblastoma tumorigenesis.
 ...
PMID:Analysis of location and integrity of the human PITSLRE (p58(cdc2L1)) genes in neuroblastoma cell genomes. 2154 74