Linked Life Data

12082532

Source:http://linkedlifedata.com/resource/pubmed/id/12082532

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2002-6-25
pubmed:abstractText
The human homologue of the Drosophila Roundabout gene DUTT1 (Deleted in U Twenty Twenty) or ROBO1 (Locus Link ID 6091), a member of the NCAM family of receptors, was recently cloned from the lung cancer tumour suppressor gene region 2 (LCTSGR2 or U2020 region) at 3p12. DUTT1 maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer lines (SCLC) and in a breast cancer line. In this report we (a) defined the genomic organization of the DUTT1 gene, (b) performed mutation and expression analysis of DUTT1 in lung, breast and kidney cancers, (c) identified tumour specific promoter region methylation of DUTT1 in human cancers. The gene was found to contain 29 exons and spans at least 240 kb of genomic sequence. The 5' region contains a CpG island, and the poly(A)(+) tail has an atypical 5'-GATAAA-3' signal. We analysed DUTT1 for mutations in lung, breast and kidney cancers, no inactivating mutations were detected by PCR-SSCP. However, seven germline missense changes were found and characterized. DUTT1 expression was not detectable in one out of 18 breast tumour lines analysed by RT-PCR. Bisulfite sequencing of the promoter region of DUTT1 gene in the HTB-19 breast tumour cell line (not expressing DUTT1) showed complete hypermethylation of CpG sites within the promoter region of the DUTT1 gene (-244 to +27 relative to the translation start site). The expression of DUTT1 gene was reactivated in HTB-19 after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The same region was also found to be hypermethylated in six out of 32 (19%) primary invasive breast carcinomas and eight out of 44 (18%) primary clear cell renal cell carcinomas (CC-RCC) and in one out of 26 (4%) primary NSCLC tumours. Furthermore 80% of breast and 75% of CC-RCC tumours showing DUTT1 methylation had allelic losses for 3p12 markers hence obeying Knudson's two hit hypothesis. Our findings suggest that DUTT1 warrants further analysis as a candidate for the tumour suppressor gene (TSG) at 3p12, a region defined by hemi and homozygous deletions and functional analysis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3020-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12082532-Animals, pubmed-meshheading:12082532-Azacitidine, pubmed-meshheading:12082532-Breast Neoplasms, pubmed-meshheading:12082532-Carcinoma, pubmed-meshheading:12082532-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:12082532-Chromosomes, Human, Pair 3, pubmed-meshheading:12082532-CpG Islands, pubmed-meshheading:12082532-DNA, Neoplasm, pubmed-meshheading:12082532-DNA Methylation, pubmed-meshheading:12082532-DNA Mutational Analysis, pubmed-meshheading:12082532-Drosophila Proteins, pubmed-meshheading:12082532-Drosophila melanogaster, pubmed-meshheading:12082532-Female, pubmed-meshheading:12082532-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12082532-Genes, Tumor Suppressor, pubmed-meshheading:12082532-Humans, pubmed-meshheading:12082532-Kidney Neoplasms, pubmed-meshheading:12082532-Loss of Heterozygosity, pubmed-meshheading:12082532-Lung Neoplasms, pubmed-meshheading:12082532-Mutation, Missense, pubmed-meshheading:12082532-Nerve Tissue Proteins, pubmed-meshheading:12082532-Promoter Regions, Genetic, pubmed-meshheading:12082532-Receptors, Immunologic, pubmed-meshheading:12082532-Sequence Homology, Nucleic Acid, pubmed-meshheading:12082532-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers.
pubmed:affiliation
Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham B15 2TT, UK. flatif@hgmp.mrc.ac.uk
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't