Linked Life Data

15870700

Source:http://linkedlifedata.com/resource/pubmed/id/15870700

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2005-7-14
pubmed:abstractText
Lung cancer is the most widely diagnosed malignancy in the world. Understanding early-stage disease will give insight into its pathogenesis. Despite the fact that pre-invasive lesions are challenging to isolate, and often yield insufficient DNA for the analysis of multiple loci, genomic profiling of such lesions will lead to the discovery of causal genetic alterations, which may be otherwise masked by the gross instability associated with tumors. In this study, we report the identification of multiple early genetic events on chromosome 5p in lung cancer progression. Using a high-resolution 5p-specific genomic array, which contains a tiling path of DNA segments for comparative genomic hybridization, nine novel minimal regions of loss and gain were discovered in bronchial carcinoma in situ (CIS) specimens. Within these regions we identified two candidate genes novel to lung cancer. The 0.27 Mbp region at 5p15.2 contains a single gene, Triple Functional Domain, which we determined to be differentially expressed in tumors. The 0.34 Mbp region at 5p13.2 contains Glial Cell Line-Derived Neurotrophic Factor (GDNF), which is a ligand for the RET oncogene product and is normally expressed during lung development (but absent in adult lung tissue). Our data showed not only that GDNF is overexpressed at the transcript level in squamous non-small-cell lung carcinoma, but also that the GDNF protein is present in early-stage lesions. Reactivation of the fetal lung expressed GDNF in early lesions and its amplification in CIS suggests an early role in tumorigenesis. These results highlight the value of examining the genomes of pre-invasive stages of cancer at tiling resolution.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4806-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Chromosome 5p aberrations are early events in lung cancer: implication of glial cell line-derived neurotrophic factor in disease progression.
pubmed:affiliation
British Columbia Cancer Research Centre, 601 West 10th Avenue, Vancouver, BC, Canada V5Z 3L1. cgarnis@bccrc.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't