Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The locus for Werner syndrome (WRN) has been localized to human chromosome 8p21 --> p12, close to the anonymous marker D8S339. A 3.1-Mb contig of yeast artificial chromosomes (YACs) was assembled around D8S339. Results from analyses of somatic cell hybrids, FISH, and physical mapping suggest the following loci order: tel-NEFL-D8S131-D8S339-[D8S540/GSR]-D8S124 -D8S259-D8S87-FGFR1-cen. Close physical linkage between D8S540 and GSR was established within a DNA fragment of 200 kb. These two loci are not more than 400 kb from D8S339. In addition, D8S339, D8S540, D8S124, and GSR are within 1.1 Mb. These data establish a primary physical map of the Werner syndrome region and identify useful YAC clones for the isolation of new markers and of the corresponding gene.
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PMID:A 3.1-Mb YAC contig within the Werner syndrome region, on the short arm of human chromosome 8. 856 38

Rearrangements of bands 14q32.3 and 19p13.3 and preferential deletion of the short arm of chromosome 1 were nonrandom chromosomal abnormalities in MM and PCL, warranting further investigation at the molecular level. From the viewpoint of clinical relevance, chromosome 14q32 translocation seems to be associated with leukemic manifestation, level of LDH, and shorter survival period from the time of chromosomal analysis. However, these results were obtained from patients with advanced disease, most of whom had already been treated with alkylating agents prior to cytogenetic analysis. To investigate the karyotypes of MM in the early stage and to determine correlations with clinical features, non-dividing cells should be analyzed. For this purpose, interphase FISH and/or comparative genomic hybridization are promising procedures to detect genomic alterations in early multiple myeloma.
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PMID:Non-random chromosomal rearrangements and their implications in clinical features and outcome of multiple myeloma and plasma cell leukemia. 890 65

Molecular techniques are becoming increasingly important in the analysis of NHL, both for diagnostic purposes and in order to evaluate prognosis accurately. The increasing number of techniques available renders evaluation of their relative roles important and a review of their informativity in NHL at diagnosis timely. Molecular equivalents of chromosomal translocations generate either a qualitative change due to the expression of a chimaeric, relatively tumour specific, protein, such as the NPM-ALK associated with the t(2;5) in ALCL or a quantitative change in the extent, stage or site of expression of a full length protein, due to its juxtapositioning to and deregulation by an Ig or TCR gene. The latter represents errors of the somatic recombination process which lymphoid precursors undergo. In NHL, this category includes BCL1/CCND1, BCL2, BCL6 and MYC. The molecular characteristics, the functional consequences and the main clinical correlations of each of these abnormalities is reviewed. At diagnosis, immunological detection of the deregulated 'protooncogene' may well provide the simplest, most appropriate screening technique for CCND1 and NPM-ALK induced ALK expression. BCL6 abnormalities demonstrate similarities to BCL2 and MYC and a combination of immunophenotypic, FISH, Southern blot and PCR techniques are useful in their characterization. For the approximately 50% of NHL without one of the above markers, identification of a clonal Ig or TCR rearrangement can provide a useful 'pan' B or T molecular equivalent, provided that the limitations of the detection techniques are appreciated. Appropriate use of these techniques will transform our ability to classify, stratify and eventually treat in a risk adapted manner, patients with NHL.
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PMID:Practical role of molecular diagnostics in non-Hodgkin's lymphomas. 913 11

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors in affected individuals. The MEN1 locus is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis has placed the MEN1 gene within a 2-Mb interval flanked by D11S1883 and D11S449. As a step toward cloning the MEN1 gene, we have constructed a 2.8-Mb clone contig consisting of YAC and bacterial clones (PAC, BAC, and P1) for the D11S480 to D11S913 region. The bacterial clones alone represent nearly all of the 2.8-Mb contig. The contig was assembled based on a high-density STS-content analysis of 79 genomic clones (YAC, PAC, BAC, and P1) with 118 STSs. The STSs included 22 polymorphic markers and 20 transcripts, with the remainder primarily derived from the end sequences of the genomic clones. An independent cosmid contig for the 1-Mb PYGM-SEA region was also generated. Support for correctness of the 2.8-Mb contig map comes from an independent ordering of the clones by fiber-FISH. This sequence-ready contig will be a useful resource for positional cloning of MEN1 and other disease genes whose loci fall within this region.
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PMID:A 2.8-Mb clone contig of the multiple endocrine neoplasia type 1 (MEN1) region at 11q13. 920 15

The TWIST gene maps to 7p21 and mutations in the gene have been reported in the Saethre-Chotzen form of craniosynostosis. The position of the Saethre-Chotzen gene has previously been refined by FISH analysis of four patients carrying balanced translocations involving 7p21 which suggested that it was located between D7S488 and D7S503. We report here that the breakpoints in four translocation patients do not interrupt the coding sequence of the TWIST gene and thus most likely act through a positional effect. Twelve Saethre-Chotzen cases were found to have TWIST mutations. Four of these families had been used as part of the linkage study of the Saethre-Chotzen locus. The mutations detected included missense and nonsense mutations and three cases of a 21 bp duplication. Although phenotypically diagnosed as having Saethre-Chotzen syndrome, three families were found to have a pro250arg mutation of FGFR3.
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PMID:The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases. 925 86

Dysregulation of c-myc by translocation to the switch regions of the IgH locus occurs in most murine plasmacytomas. Translocations involving 14q32 have been reported in 20-40% of abnormal karyotypes from human multiple myeloma (MM), and involve a variety of loci. Using cytogenetics, FISH and a Southern blot assay, we analyzed 21 MM cells lines and one plasma cell leukemia and identified evidence of a 14q32 translocation in 20/22 samples. The partner loci involved are 11q13 in 6 (associated with cyclin D1 expression), 4p16 in 6 (associated with FGFR3 expression), unidentified in 3 and 1p13, 6, 8q24, 12q24, 16q23, and 21q22 once each. We conclude that conventional karyotypes underestimate the frequency of 14q32 translocations in MM, where they appear to be a nearly universal event. The translocations most frequently involve IgH switch regions, and include two recurrent partner loci (11q13 and 4p16) and a promiscuous array of other partner loci. Although c-myc appears to be cis-dysregulated frequently in MM, it is only rarely translocated to the IgH locus.
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PMID:IgH translocations in multiple myeloma: a nearly universal event that rarely involves c-myc. 930 53

Fibroblast growth factor-8 (Fgf8) is a recently identified growth factor that stimulates the androgen-dependent growth of mouse mammary carcinoma cells. Evidence from mouse development also shows that Fgf8 may play an important role in growth and patterning of limbs, face, and the central nervous system. We describe here the human FGF8 genomic sequence and demonstrate conservation between the human and mouse sequences, including alternatively spliced exons in the mouse. Mapping of FGF8 by FISH using an FGF8-containing bacterial artificial chromosome and by genetic linkage using a SSCP variant identified in this study is also reported and refines the FGF8 map location to 10q24. Since FGF8 maps to the same chromosomal region as FGFR2, has indeed been shown to be a ligand for FGFR2, and has an expression pattern consistent with limb and craniofacial anomalies, we have screened two kindreds with Pfeiffer syndrome that were previously linked to markers from 10q24-25 and a large number of individuals with craniosynostosis and limb anomalies for mutations in the coding sequence of FGF8. While no such mutations were identified, a rare polymorphic variant, consisting of an 18-base-pair (six-amino-acid) duplication in exon 1c, is reported that apparently has no clinical effect. Our exclusionary data suggest that mutations in FGF8 would be, at best, an infrequent cause of such disorders.
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PMID:Genomic structure, sequence, and mapping of human FGF8 with no evidence for its role in craniosynostosis/limb defect syndromes. 933 70

GDNFR-alpha is a glycosyl-phosphotidylinositol-linked receptor for glial cell line-derived neurotrophic factor (GDNF). GDNF binds to GDNFR-alpha and this complex, in turn, is believed to interact with the RET receptor tyrosine kinase to effect downstream signalling. GDNFR-alpha belongs to a novel gene family without strong homology to known genes. Thus, little information has been available to help predict genomic structure or location of this gene. In this study, the genomic organization of human GDNFR-alpha was delineated through a combination of PAC clone characterization, long distance PCR and sequence analyses. Exon-intron boundaries were defined by comparing the size and sequence of the genomic PCR products to those predicted by the cDNA sequence. The human GDNFR-alpha gene comprises 9 exons. GDNFR-alpha PAC clones were used for FISH analysis to map this gene to 10q26.
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PMID:Genomic structure and chromosomal localization of the human GDNFR-alpha gene. 948 5

Loss of DNA sequences within human chromosomal band 7q31.2 is frequently observed in a number of different solid tumors including breast, prostate, and ovarian cancer. This chromosomal band also contains the common fragile site, FRA7G. Many of the common fragile sites occur within chromosomal regions that are frequently deleted during tumor formation but their precise position, relative to the chromosome breakpoints and deletions, has not been defined for the majority of the fragile sites. Because the frequency of expression of FRA7G is low, we analyzed the expression of FRA7G in a chromosome 7-only somatic cell hybrid (hamster-human). YAC clones defining a contig spanning 7q31.2 were then used as FISH probes against metaphase spreads prepared from the hybrid cells after aphidicolin induction. This analysis quickly revealed whether a specific YAC clone mapped proximal, distal, or actually spanned the region of decondensation/breakage of FRA7G. By using this approach, we have identified several overlapping YAC clones that clearly span FRA7G. Interestingly, these clones map precisely to the common region of LOH in breast cancer and prostate cancer. In addition, the MET oncogene is contained within the three YACs that span FRA7G.
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PMID:Fish mapping of YAC clones at human chromosomal band 7q31.2: identification of YACS spanning FRA7G within the common region of LOH in breast and prostate cancer. 949 27

Little information is available on the molecular mechanisms underlying neuroendocrine tumorigenesis. To obtain an overview of the genomic imbalances characterizing these tumors, we studied 20 benign or malignant sporadic endocrine gastroenteropancreatic tumors by comparative genomic hybridization. Chromosomal imbalances were found in all tumors. Gains of chromosomal material were more frequent than losses. The most frequent gains were of chromosomes and chromosome arms 5 (55%), 14 (55%), 17q (55%), and 7 (50%). Losses were most frequent from 11q (30%) and 16p (30%). Gains of chromosome 5 did not occur in nonmetastatic tumors, whereas losses of 9p were observed exclusively in intestinal tumors. In addition, we found two high-level amplifications, of 17q11-21 and 19q13. A complementary FISH analysis revealed that the gain in 17q11-21 included amplification of the protooncogene HER2/neu. As in multiple endocrine neoplasia type-1-associated tumors, deletions of chromosome band 11q13 appear to be involved in the development of sporadic digestive tract neuroendocrine tumors, but our results suggest that other chromosomal regions are also involved.
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PMID:Comparative genomic hybridization analysis of sporadic neuroendocrine tumors of the digestive system. 959 34


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