Methods to determine a chemotherapeutic regimen based on the loss of heterozygosity in the thymidylate synthase locus

摘要

Method for predicting a response of a cancer patient to a chemotherapeutic regimen, in which the regimen comprises a thymidylate synthase (TS) inhibitor, said method comprising: (a) determining the genotype of the tandem repeat polymorphism in the enhancer region of the TS gene (TSER) in the patient's normal tissue; (b) determine said genotype in the patient's tumor tissue; (c) compare the normal tissue genotype with the tumor tissue genotype to determine if it has occurred in the tumor tissue a loss of heterozygosity in TSER; and (d) if there is a loss of heterozygosity, predict a response to the chemotherapeutic regimen based on the loss of heterozygosity in the tumor sample, in which (i) a determination of the presence of an allele with triple recurrence in TSER (3R) predicts a direct negative effect on the tumor's response to the chemotherapeutic regimen; (ii) a determination of the loss of heterozygosity from 2R / 3R in normal tissue to 2R / loss in tumor tissue predicts a greater sensitivity of the tumor to the chemotherapeutic regimen with respect to the sensitivity of a tumor that has a 2R / 3R genotype; and / or (iii) a determination of the loss of heterozygosity from 2R / 3R in normal tissue to 3R / loss in tumor tissue predicts a tumor sensitivity to the chemotherapeutic regimen similar to that of a tumor that has a 3R / 3R genotype.