Methods and materials for assessing loss of heterozygosity
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 for detecting DNA from a cancer cell, comprising:
(A) extracting DNA from a sample comprising a cancer cell,
(B) genotyping a plurality of single nucleotide polymorphism (SNP) loci in at least five pairs of human chromosomes other than a human X/Y sex chromosome pair in DNA from the sample, wherein the SNP loci are spaced about 25 kb to about 100 kb apart on one or more of the at least five pairs of human chromosomes, wherein genotyping comprises
(i) enriching the sample for DNA molecules each comprising at least one locus from the plurality of SNP loci, and wherein the enriching is achieved using at least 500 oligonucleotide capture probes, and
(ii) detecting either a homozygous genotype or heterozygous genotype at each locus from the plurality of SNP loci, wherein the plurality of SNP loci comprises at least 1,000 SNP loci,
wherein the homozygous genotype indicates the presence of a loss of heterozygosity (LOH) Region, wherein the LOH Region is defined as a genomic region wherein all SNP loci in the genotyped region are homozygous, and wherein such genomic region is equal to or longer than a first length but shorter than the length of the whole chromosome containing the genomic region, and wherein the first length is at least 1.5 megabases;
thereby detecting DNA from the sample comprising the presence of a LOH region.
2 . The method of claim 1 , wherein step (B) comprises genotyping a plurality of SNP loci in at least 10 pairs of human chromosomes other than a human X/Y sex chromosome pair in DNA from the sample.
3 . The method of claim 1 , wherein the length of the first length is at least 5 megabases.
4 . The method of claim 1 , wherein the length of the first length is at least 15 megabases.
5 . The method of claim 1 , wherein the plurality of single nucleotide polymorphism loci comprises at least 2,500 single nucleotide polymorphism loci.
6 . The method of claim 1 , wherein the plurality of single nucleotide polymorphism loci comprises at least 10,000 single nucleotide polymorphism loci.
7 . The method of claim 1 , wherein the plurality of single nucleotide polymorphism loci comprises at least 25,000 single nucleotide polymorphism loci.
8 . The method of claim 1 , wherein the plurality of single nucleotide polymorphism loci comprises at least 50,000 single nucleotide polymorphism loci.
9 . The method of claim 1 , wherein the cancer cell is a breast cancer cell or an ovarian cancer cell.