DNA Mutations Identified in Chemotherapy-Resistant Cancer Cells

The development of chemotherapy resistance was investigated in an in-vitro model of ovarian cancer.

Array comparative genomic hybridization (aCGH), gene expression profiling, and molecular cytogenetic analyses were used for genome profiling in cisplatin-resistant ovarian cancer cells. aCGH detects genomic aberrations not evident by traditional cytogenetic techniques, whereas cytogenetic analysis detects structural changes not apparent by aCGH. Genomic interrogation that applies aCGH, gene expression profiling, and molecular cytogenetic analyses in a parallel fashion yields a much more comprehensive genomic profile to assess the chromosomal abnormalities associated with disease.

Using Agilent (Santa Clara, CA, USA) microarrays, scientists from the division of applied molecular oncology, Ontario Cancer Institute, Princess Margaret Hospital (OCI; Toronto, Canada) analyzed copy number and gene expression concurrently in an in-vitro model of ovarian cancer. The third component of the study included advanced molecular cytogenetic analyses. The results of this multi-front approach to genomic profiling enabled the group to identify relationships between particular genomic aberrations and expressed loci, and to reveal the origin of acquired chromosomal mutations in a drug-resistant cell line.

The study is available online in April 2008, in an early edition of the journal Genes Chromosomes Cancer.


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Ontario Cancer Institute, Princess Margaret Hospital