Tumor genotyping

In conclusion, contradictory data have been published for P-gp genotypes. The studies discussed are evaluating different regimens and tumor types. The same protein can have different pharmacokinetic and pharmacodynamic effects in different tumors and in response to different drugs. Therefore, every tumor type and drug has to be investigated independently. 

Keywords Cancer genotyping germline mutation polymorphism tumor. 

DNA from any source can be utilized for pharmacogenetics research, including germline and tumor sources. Immortalized cell lines can provide an almost infinite DNA resource, and genotyping of Epstein-Barr virus (EBV)-transformed immortalized lymphoblastoid cells has demonstrated similar allele frequencies to equivalent... 

Rae, J. M., Cordero, K. E., Scheys, J. O., Lippman, M. E., Flockhart, D. A., and Johnson, M. D. (2003) Genotyping for polymorphic drug metabolizing enzymes from paraffin-embedded and immunohistochemically stained tumor samples. Pharmacogenetics. 13, 501-507. 

Dolma S, Lessnick SL, Hahn WC et al (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3 285-296... 

While no biopharmaceutical is approved with the requirement of genotyping as a part of its therapeutic indication, a recently approved monoclonal antibody therapy against breast cancer, trastuzumab (Herceptin), is indicated only for those tumors measurably expressing the protein expressed by the gene erbB-2. Because the oncogene product of erbB-2 is elevated... 

The amount of DNA available from tissue samples, especially samples from tumor biopsies, is usually limited. Fortunately, whole-genome amplification has been developed to generate micrograms of DNA for further analysis (52,53). We found similar genotype calls and copy number changes in whole-genome amplified DNA with that using unamplified DNA, as determined by a 10 K SNP array analysis (30). 

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