A METHOD FOR GENERATING REFERENCE CONTROLS FOR PHARMACOGENOMIC TESTING

Reference controls for use with pharmacogenomic testing, and methods for their identification, preparation, and use, are disclosed. The reference controls can confirm that pharmacogenomic testing correctly identifies individuals that do or do not have the mutation of interest, in both clinical trial and patient treatment settings. The reference controls can be selected to include one or more mutations to be identified, and prescreened to confirm that they bind to one or more of the primers used in the pharmacogenomic testing. The reference controls are human genomic DNA that includes certain identified polymorphisms (mutations) of interest, ideally derived from individuals, pre-selected and optionally properly consented, which have one or more of the polymorphism(s) of interest. The reference controls can be prepared by targeted pre-screening of human patients, by examining the genotype or genetic profile of the patients, isolating cells with the desired mutation, optionally immortalizing the cells, and obtaining DNA from the cells. The prescreening of prospective donors can be targeted based on any of a number of factors, such as genes of interest, mutations within the genes of interest, and membership in a specific ethnic or disease state population. The genomic DNA can be pre-screened for its ability to be detected, using a standard pharmacogenomic test, as including a specific mutation. Examples of mutations of interest include those present in a Phase I or Phase Il metabolic enzyme such as CYP2D6, CYP2C 19, CYP2C9, CYP2C8, and CYP3A5, CYP3A4, CYP2A6, CYP2B6, UGT1A1, DPD, ERCC1, MDR1, ADH2, NAT1 and NAT2 or any other metabolic or disease gene. L'invention concerne des témoins de référence à utiliser avec un essai pharmacogénomique, et des procédés pour leur identification, préparation, et utilisation. Les témoins de référence peuvent confirmer qu'un essai pharmacogénomique identifie de manière correcte des individus qui ont ou n'ont pas la mutation concernée, à la fois dans les paramètres d'essai clinique et de traitement de patient. Les témoins de référence peuvent être sélectionnés pour inclure une ou plusieurs mutations à identifier, et précriblés pour confirmer qu'ils se lient à une ou plusieurs des amorces utilisées dans l'essai pharmacogénomique. Les témoins de référence sont un ADN génomique humain qui comprend certains polymorphismes (mutations) d'intérêt, dérivés idéalement d'individus présélectionnés et ayant facultativement correctement cons