Association of a single nucleotide polymorphic variation in the human chromosome 19q13.3 with drug responses in the NCI60 cell lines.
We studied the importance of certain polymorphisms on human chromosome 19q13.3 for drug sensitivity in human tumor cell cultures. NCI60 is a panel of 60 established tumor-derived cell lines, which have been tested for their sensitivity to tens of thousands of different drugs. Here we investigate the correlations between the responses of the NCI60 cells to different anticancer drugs and their respective alleles of five DNA polymorphisms located in a cancer-related chromosomal area. One polymorphism, located in the 5' noncoding region of the gene ASE-1, alias CD3EAP, proved to be associated with drug sensitivity (P = 0.025). The same polymorphism has previously been associated with treatment response of multiple myeloma after bone marrow ablation. The polymorphism ASE-1-e1 was of importance for the drug response in the human cancer cell lines investigated and could eventually become important for individualized drug treatment in humans.
Nissen
Kari K
KK
Department of Human Genetics, University of Aarhus, Aarhus C, Denmark.
Vogel
Ulla
U
Nexø
Bjørn A
BA
D045744:Cell Line, Tumor / Q000187:drug effects*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics* / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics; D005091:Exons / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D012318:RNA Polymerase I; D012097:Repressor Proteins
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; C119975:POLR1G protein, human; D012318:RNA Polymerase I; C071447:ERCC1 protein, human; D004720:Endonucleases