Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors
AssigneesInstitut Curie, Inserm (Institut National De La Sante Et De La Recherche Medicale)
InventorsElodie Manie, Marc-Henri Stern, Tatiana Popova
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Abstract
Methods for detecting inactivation of the DNA Homologous Recombination pathway in a patient, and in particular for detecting BRCA1 inactivation, are provided.
Claims18
A method for predicting tumor deficiency in the DNA homologous recombination (HR) pathway in a patient suffering from cancer, comprising the step of quantifying the number of rearrangements in the genomic DNA of a tumor sample obtained from said patient, wherein the number of rearrangements corresponds to the number, per genome, of breakpoints resulting in segments of at least 3 megabases.
A method for predicting tumor deficiency in the DNA homologous recombination (HR) pathway in a patient suffering from cancer, comprising the steps consisting of:
- determining the ploidy of the tumor sample;
- quantifying the number of rearrangements in the genomic DNA of a tumor sample obtained from said patient;
- comparing the number of rearrangements per genome to a reference, wherein a number of rearrangements resulting in segments of at least 3 megabases superior to said reference is indicative of HR deficiency.
A method for treating cancer in a patient, comprising the steps of:
- quantifying the number of rearrangements in the genomic DNA of a tumor sample obtained from said patient, wherein the number of rearrangements corresponds to the number, per genome, of breakpoints resulting in segments of at least 3 megabases, preferably at least 4 megabases, even more preferably at least 5, 6, 7, 8 9, 10, 11 12, 13, 14, 15, 16, 17, 18, 19 or 20 megabases.
- comparing said number of rearrangements to a predetermined reference;
- administering a therapeutically effective amount of a PARP inhibitor and/or an alkylating agent, if said patient has a number of rearrangements superior to said reference.
Dependencies are inferred from the claim text.