Linked Life Data

12853973

Source:http://linkedlifedata.com/resource/pubmed/id/12853973

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2003-7-10
pubmed:abstractText
Tumors with defects in mismatch repair (MMR) show fewer chromosomal changes by cytogenetic analyses than most solid tumors, suggesting that a greater proportion of the alterations required for malignancy occur in genes with nucleotide sequences susceptible to errors normally corrected by MMR. Here, we used genome-wide microarray comparative genomic hybridization to carry out a higher resolution evaluation of the effect of MMR competence on genomic alterations occurring in 20 cell lines and to determine if characteristic aberrations arise in MMR-proficient and -deficient HCT116 cells undergoing selection for methotrexate resistance. We observed different spectra of aberrations in MMR-proficient compared to -deficient cell lines, as well as among cell lines with different types of MMR-deficiency. We also observed different genetic routes to drug resistance. Resistant MMR-deficient cells most frequently displayed no copy number alterations (16/29 cell pools), whereas all MMR-proficient cells had unique abnormalities involving chromosome 5, including amplicons centered on the target gene, DHFR and/or a neighboring novel locus (7/13 pools). These observations support the concept that tumor genomes are shaped by selection for alterations that promote survival and growth advantage, as well as by the particular dysfunctions in genes responsible for maintenance of genetic integrity.
pubmed:grant
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
10
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4370-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Shaping of tumor and drug-resistant genomes by instability and selection.
pubmed:affiliation
Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143-0808, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.