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    Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer.

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    Authors
    White, Gavin R M
    Varley, Jennifer
    Heighway, Jim
    Affiliation
    CRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
    Issue Date
    1998-12-31
    
    Metadata
    Show full item record
    Abstract
    We have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour.
    Citation
    Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. 1998, 17 (26):3513-9 Oncogene
    Journal
    Oncogene
    URI
    http://hdl.handle.net/10541/93114
    DOI
    10.1038/sj.onc.1202487
    PubMed ID
    10030676
    Type
    Article
    Language
    en
    ISSN
    0950-9232
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.onc.1202487
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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