Methods and materials for assessing loss of heterozygosity

Abstract

This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of a loss of heterozygosity (LOH) signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an LOH signature are provided. Materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen also are provided.

What is claimed is: 
     
         1 . A method of predicting a cancer patient's response to a cancer treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, and/or a PARP inhibitor, said method comprising:
 determining, in the cancer cell, the total number of LOH regions in at least one pair of human chromosomes of said cancer cell that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region, wherein said at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein said first length is about 15 or more megabases, wherein the cancer cell is selected from the group consisting of breast cancer cells, ovarian cancer cells, leukemia cancer cells, esophageal cancer cells, lung cancer cells, and prostate cancer cells; and   correlating said total number that is greater than a reference number with an increased likelihood that said cancer patient will respond to said cancer treatment regimen.   
     
     
         2 . The method of  claim 1 , wherein said LOH regions or Indicator LOH Regions are determined in at least two, five, ten or 21 pairs of human chromosomes. 
     
     
         3 . The method of  claim 1 , wherein said total number of LOH regions or Indicator LOH Regions is 9, 15, 20 or more. 
     
     
         4 . The method of  claim 1 , wherein said reference number is 6, 7, 8, 9, 10, 11, 12 or 13 or greater. 
     
     
         5 . The method of  claim 1 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         6 . The method of  claim 1 , wherein said DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, said anthracycline is epirubicin or doxorubicin, said topoisomerase I inhibitor is campothecin, topotecan, or irinotecan, or said PARP inhibitor is iniparib, olaparib or veliparib. 
     
     
         7 . A cancer treatment comprising one or more drugs chosen from the group consisting of DNA damaging agents, anthracyclines, topoisomerase I inhibitors, and PARP inhibitors for use in treating cancer in a patient having an increased likelihood of response to said treatment, wherein the determination of whether or not the patient has an increased likelihood of response to said treatment is carried out by the method of  claim 1 . 
     
     
         8 . A method of predicting a cancer patient's response to a treatment regimen including paclitaxel or docetaxel, comprising:
 determining, in the cancer cell, the total number of LOH regions in at least one pair of human chromosomes of said cancer cell that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region, wherein said at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein said first length is about 15 or more megabases, wherein the cancer cell is selected from the group consisting of breast cancer cells, ovarian cancer cells, leukemia cancer cells, esophageal cancer cells, lung cancer cells, and prostate cancer cells; and   correlating said total number that is greater than a reference number with an increased likelihood that said cancer patient will not respond to a treatment regimen including paclitaxel or docetaxel.   
     
     
         9 . The method of  claim 8 , wherein said LOH regions or Indicator LOH Regions are determined in at least two, five, ten or 21 pairs of human chromosomes. 
     
     
         10 . The method of  claim 8 , wherein said total number of LOH regions or Indicator LOH Regions is 9, 15, 20 or more. 
     
     
         11 . The method of  claim 8 , wherein said reference number is 6, 7, 8, 9, 10, 11, 12 or 13 or greater. 
     
     
         12 . The method of  claim 8 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         13 . A cancer treatment comprising one or more drugs chosen from the group consisting of DNA damaging agents, anthracyclines, topoisomerase I inhibitors, and PARP inhibitors for use in treating cancer in a patient having an increased likelihood of response to said treatment, wherein the determination of whether or not the patient has an increased likelihood of response to said treatment is carried out by the method of  claim 8 . 
     
     
         14 . A system for determining LOH status of a cancer cell of a cancer patient, comprising:
 (a) a sample analyzer configured to produce a plurality of signals about genomic DNA, wherein said signals identify the homozygous or heterozygous nature of loci of at least one pair of human chromosomes of said cancer cell, and wherein the cancer cell is selected from the group consisting of breast cancer cells, ovarian cancer cells, leukemia cancer cells, esophageal cancer cells, lung cancer cells, and prostate cancer cells, and   (b) a computer sub-system programmed to calculate, based on said plurality of signals, the number of Indicator LOH Regions in said at least one pair of human chromosomes, wherein said Indicator LOH Regions are LOH regions that are in a pair of human chromosomes other than the human X/Y sex chromosome pair, and are characterized by LOH with a length of about 15 or more megabases but shorter than the length of the whole chromosome containing the LOH regions, and wherein said computer sub-system is programmed to compare said number of Indicator LOH Regions to a reference number to determine a likelihood that said cancer patient will respond to cancer treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, or a PARP inhibitor.   
     
     
         15 . The system of  claim 14 , wherein said LOH regions or Indicator LOH Regions are determined in at least two, five, ten or 21 pairs of human chromosomes. 
     
     
         16 . The system of  claim 14 , wherein said total number of LOH regions or Indicator LOH Regions is 9, 15, 20 or more. 
     
     
         17 . The system of  claim 14 , wherein said reference number is 6, 7, 8, 9, 10, 11, 12 or 13 or greater. 
     
     
         18 . The system of  claim 14 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         19 . The system of  claim 14 , wherein said Indicator LOH Regions are not in human chromosome 17. 
     
     
         20 . The system of  claim 14 , wherein said DNA damaging agent is a platinum-based chemotherapy drug, said anthracycline is epirubicin or doxorubicin, said topoisomerase I inhibitor is campothecin, topotecan, or irinotecan, or said PARP inhibitor is iniparib, olaparib or veliparib.