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.

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 a cancer cell from said cancer patient, the number of LOH regions in at least one pair of human chromosomes of a cancer cell of said cancer patient 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 1.5 or more megabases; 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 . A method of predicting a cancer patient's response to a treatment regimen, comprising:
 determining, in a cancer cell from said cancer patient, the total number of LOH regions in at least one pair of human chromosomes of a cancer cell of said cancer patient 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 1.5 or more megabases; 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.   
     
     
         3 . A method of treating cancer, comprising:
 (a) determining, in a cancer cell from a cancer patient or genomic DNA obtained therefrom, the total number of LOH regions in at least one pair of human chromosomes of the 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 1.5 or more megabases; and   (b) administering to said cancer patient a cancer treatment regimen comprising one or more drugs chosen from the group consisting of DNA damaging agents, anthracyclines, topoisomerase I inhibitors, and PARP inhibitors, if said total number of LOH regions is greater than a reference number.   
     
     
         4 . The method of  claim 1 , wherein said LOH regions are determined in at least two, five, ten or 21 pairs of human chromosomes. 
     
     
         5 . The method of  claim 2 , wherein said LOH regions are determined in at least two, five, ten or 21 pairs of human chromosomes. 
     
     
         6 . The method of  claim 3 , wherein said LOH regions are determined in at least two, five, ten or 21 pairs of human chromosomes. 
     
     
         7 . The method of  claim 1 , wherein said cancer cell is an ovarian, breast, or esophageal cancer cell. 
     
     
         8 . The method of  claim 2 , wherein said cancer cell is an ovarian, breast, or esophageal cancer cell. 
     
     
         9 . The method of  claim 3 , wherein said cancer cell is an ovarian, breast, or esophageal cancer cell. 
     
     
         10 . The method of  claim 1 , wherein said total number of LOH regions is 9, 15, 20 or more. 
     
     
         11 . The method of  claim 2 , wherein said total number of LOH regions is 9, 15, 20 or more. 
     
     
         12 . The method of  claim 3 , wherein said total number of LOH regions is 9, 15, 20 or more. 
     
     
         13 . The method of  claim 1 , wherein said first length is about 6, 12, or 15 or more megabases. 
     
     
         14 . The method of  claim 2 , wherein said first length is about 6, 12, or 15 or more megabases. 
     
     
         15 . The method of  claim 3 , wherein said first length is about 6, 12, or 15 or more megabases. 
     
     
         16 . The method of  claim 1 , wherein said reference number is 6, 7, 8, 9, 10, 11, 12 or 13 or greater. 
     
     
         17 . The method of  claim 2 , wherein said reference number is 6, 7, 8, 9, 10, 11, 12 or 13 or greater. 
     
     
         18 . The method of  claim 3 , wherein said reference number is 6, 7, 8, 9, 10, 11, 12 or 13 or greater. 
     
     
         19 . The method of  claim 1 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         20 . The method of  claim 2 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         21 . The method of  claim 3 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         22 . The method of  claim 2 , wherein said DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, said anthracycline is epirubincin or doxorubicin, said topoisomerase I inhibitor is campothecin, topotecan, or irinotecan, or said PARP inhibitor is iniparib, olaparib or velapirib. 
     
     
         23 . The method of  claim 3 , wherein said DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, said anthracycline is epirubincin or doxorubicin, said topoisomerase I inhibitor is campothecin, topotecan, or irinotecan, or said PARP inhibitor is iniparib, olaparib or velapirib.