METHODS AND MATERIALS FOR ASSESSING HOMOLOGOUS RECOMBINATION DEFICIENCY
This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of homologous recombination deficiency (HRD) or an HRD signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an HRD 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 - 36 . (canceled)
37 . A method for treating cancer, the method comprising administering a treatment regimen comprising a DNA damaging agent, anthracycline, topoisomerase I inhibitor, or PARP inhibitor to a patient; wherein a specimen obtained from the patient comprises a cancer cell having at least 30 chromosomal aberrations that are any combination comprising at least one each of (a) genomic regions of loss of heterozygosity equal to or longer than a first length but shorter than the length of the whole chromosome, and wherein the first length is at least 1.5 megabases; (b) genomic regions of allelic imbalance that extend to one of the subtelomeres, do not cross the centromere and are equal to or longer than a second length that is at least 1.5 megabases; and (c) copy number transitions along the length of a chromosome located between two regions, each such region being longer than a third length that is at least 5 megabases, after filtering out copy number transitions along the length of a chromosome located between two regions, each such region being shorter than a fourth length that is at most 4 megabases.
38 . A method for treating cancer, the method comprising administering a treatment regimen comprising a DNA damaging agent, anthracycline, topoisomerase I inhibitor, or PARP inhibitor to a patient; wherein at least 30 chromosomal aberrations have been detected in a specimen obtained from the patient comprising a cancer cell; and wherein the chromosomal aberrations are any combination comprising at least one each of (a) genomic regions of loss of heterozygosity equal to or longer than a first length but shorter than the length of the whole chromosome, and wherein the first length is at least 1.5 megabases; (b) genomic regions of allelic imbalance that extend to one of the subtelomeres, do not cross the centromere and are equal to or longer than a second length that is at least 1.5 megabases; and (c) copy number transitions along the length of a chromosome located between two regions, each such region being longer than a third length that is at least 5 megabases, after filtering out copy number transitions along the length of a chromosome located between two regions, each such region being shorter than a fourth length that is at most 4 megabases.
39 . A method for treating cancer, the method comprising administering a treatment regimen comprising a DNA damaging agent, anthracycline, topoisomerase I inhibitor, or PARP inhibitor to a patient; wherein a specimen obtained from the patient comprising a cancer cell or genomic DNA extracted therefrom has been analyzed to detect any combination of chromosomal aberrations comprising at least one each of (a) genomic regions of loss of heterozygosity equal to or longer than a first length but shorter than the length of the whole chromosome, and wherein the first length is at least 1.5 megabases; (b) genomic regions of allelic imbalance that extend to one of the subtelomeres, do not cross the centromere and are equal to or longer than a second length that is at least 1.5 megabases; and (c) copy number transitions along the length of a chromosome located between two regions, each such region being longer than a third length that is at least 5 megabases, after filtering out copy number transitions along the length of a chromosome located between two regions, each such region being shorter than a fourth length that is at most 4 megabases; and wherein at least 30 such chromosomal aberrations were detected in the sample.
40 . The method of claim 37 , wherein the cancer is selected from ovarian cancer, breast cancer, and esophageal cancer.
41 . The method of claim 38 , wherein the cancer is selected from ovarian cancer, breast cancer, and esophageal cancer.
42 . The method of claim 39 , wherein the cancer is selected from ovarian cancer, breast cancer, and esophageal cancer.
43 . The method of claim 37 , wherein the treatment regimen comprises a PARP inhibitor.
44 . The method of claim 38 , wherein the treatment regimen comprises a PARP inhibitor.
45 . The method of claim 39 , wherein the treatment regimen comprises a PARP inhibitor.
46 . The method of claim 37 , wherein the PARP inhibitor is olaparib or velapirib.
47 . The method of claim 38 , wherein the PARP inhibitor is olaparib or velapirib.
48 . The method of claim 39 , wherein the PARP inhibitor is olaparib or velapirib.
49 . The method of claim 37 , wherein the DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, the anthracycline is epirubincin or doxorubicin, or the topoisomerase I inhibitor is campothecin, topotecan, or irinotecan.
50 . The method of claim 38 , wherein the DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, the anthracycline is epirubincin or doxorubicin, or the topoisomerase I inhibitor is campothecin, topotecan, or irinotecan.
51 . The method of claim 39 , wherein the DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, the anthracycline is epirubincin or doxorubicin, or the topoisomerase I inhibitor is campothecin, topotecan, or irinotecan.
52 . The method of claim 38 , wherein the chromosomal aberrations were detected in the specimen by detecting the number of copy number variations per genome by sequencing genomic regions comprising at least 1,000 single nucleotide polymorphism loci across ten pairs of human chromosomes, wherein the single nucleotide polymorphism loci are located on average at most every 500 kb within each chromosome of the ten pairs of human chromosomes.
53 . The method of claim 39 , wherein the specimen obtained from the patient or DNA extracted therefrom has been analyzed to detect the number of copy number variations per genome by sequencing genomic regions comprising at least 1,000 single nucleotide polymorphism loci across ten pairs of human chromosomes, wherein the single nucleotide polymorphism loci are located on average at most every 500 kb within each chromosome of the ten pairs of human chromosomes.