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 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 derived from said cancer cell, wherein said signals identify the homozygous or heterozygous nature of loci of at least one pair of human chromosomes of said DNA, 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 1.5 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 that is at least 6 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.   
     
     
         2 . The system 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 system of  claim 1 , wherein said total number of LOH regions or Indicator LOH Regions is 9, 15, 20 or more. 
     
     
         4 . The system of  claim 1 , wherein said first length is or said Indicator LOH Regions have a length of about 6, 12, or 15 or more megabases. 
     
     
         5 . The system of  claim 1 , wherein said reference number is at least 7, 8, 9, 10, 11, 12 or 13. 
     
     
         6 . The system of  claim 1 , wherein said at least one pair of human chromosomes is not human chromosome 17. 
     
     
         7 . The system of  claim 1 , wherein said Indicator LOH Regions are not in human chromosome 17. 
     
     
         8 . The system of  claim 1 , 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.