Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors

Abstract

The invention relates to methods for detecting inactivation of the DNA Homologous Recombination pathway in a patient, and in particular for detecting BRCA1 inactivation.

1 . A method for treating cancer, the method comprising a therapeutically effective amount of a PARP inhibitor and/or an alkylating agent to a human patient identified as having, in a tumor sample obtained from the patient, a number, per genome, of large scale transitions (LSTs) greater than a predetermined threshold number of LSTs, wherein an LST is a breakpoint between two genomic regions of different copy number, each such genomic region greater than or equal to 3 and less than 6 megabases long. 
     
     
         2 . The method of  claim 1 , wherein said PARP inhibitor and/or alkylating agent is selected from the group consisting of iniparib, olaparib, rucaparib, CEP 9722, MK 4827, BMN-673, 3-aminobenzamide, platinum complexes, chlormethine, chlorambucil, melphalan, cyclophosphamide, ifosfamide, estramustine, carmustine, lomustine, fotemustine, streptozocin, busulfan, pipobroman, procarbazine, dacarbazine, thiotepa and temozolomide. 
     
     
         3 . The method of  claim 1 , wherein the cancer is selected from breast cancer, ovary cancer, pancreas cancer, head and neck carcinoma and melanoma. 
     
     
         4 . The method of  claim 1 , wherein the cancer is breast cancer. 
     
     
         5 . The method of  claim 1 , wherein the cancer is basal-like breast cancer. 
     
     
         6 . The method of  claim 1 , wherein the patient is identified by detecting, in the tumor sample, the number of LSTs per genome. 
     
     
         7 . The method of  claim 6 , wherein the number of LSTs per genome is detected by detecting copy number for at least 500 Single Nucleotide Polymorphism (SNP) loci. 
     
     
         8 . The method of  claim 6 , wherein the number of LSTs per genome is detected by detecting copy number for at least 3,000 Single Nucleotide Polymorphism (SNP) loci. 
     
     
         9 . The method of  claim 6 , wherein the number of LSTs per genome is detected by comparative genomic hybridization (CGH) array, Single Nucleotide Polymorphism (SNP) array, or sequencing of polymorphic loci.