Method for assessing homologous recombination deficiency in ovarian cancer cells
AssigneesZentrum FamiliäRer Brust- Und Eierstockkrebs UniversitäTsklinik KöLn, Stichting Het Netherlands Kanker Insituut - Antoni Van Leeuwenhoek Ziekenhuis
InventorsRita SCHMUTZLER, Philip SCHOUTEN, Eric HAHNEN, Sabine LINN
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Abstract
Provided are methods involved in assessing homologous recombination deficiency (HRD) status in a patient having ovarian cancer based on the determination of copy number variations (CNVs) in a genomic locus. Furthermore methods for predicting a patient's response to an anti-cancer therapy and thus to the identification of ovarian cancer patients likely to respond to a particular cancer treatment regime based on their HRD status are provided.
Claims17
An in vitro method of determining homologous recombination (HR) deficiency status in a subject having ovarian cancer, wherein the method includes the following steps:
- (a) determining copy number variation (CNV) of a genomic locus in a DNA test sample of cancer cells from the subject, wherein the genomic locus is selected from a pool of genomic loci comprising or consisting of the loci set forth in Table 1 and/or Table 2;
- wherein similarity between the CNVs of the pool of genomic loci in the DNA test sample and the CNVs of the pool of genomic loci of a reference sample of BRCA-like mutated cancer cells identifies the subject as HR deficient;
- and/or similarity between the CNVs in the pool of genomic loci in the DNA of the test sample and the CNVs in the pool of genomic loci of the control sample of BRCA non-mutated cancer cells identifies the subject as not being HR deficient, wherein similarity is the distance measure between centroids of the control sample, the reference sample, and the test sample and wherein a similarity score is calculated by comparison of the shrunken centroids of the test sample with the shrunken centroids of the reference sample and of the control sample, wherein the shrunken centroids are derived from the CNVs of the genomic loci;
- and optionally
- (b) transmitting the result to the subject or a third party.
An in vitro method of determining homologous recombination (HR) deficiency status in a subject having ovarian cancer, wherein the method includes the following steps:
- (a) determining copy number variation (CNV) of a genomic locus in a DNA test sample of cancer cells from the subject, wherein the locus is selected from a pool of genomic loci comprising or consisting of the loci set forth in Table 1 and/or the loci set forth in Table 2,
- (b) providing a shrunken centroid value which is derived from the CNV of the genomic locus;
- and
- wherein a posterior probability score of ≥0.5 identifies the subject as HR deficient;
- and/or wherein a posterior probability score of <0.5 identifies the subject as not being HR deficient, wherein the posterior probability score is obtainable by comparison of the shrunken centroid values derived from the CNVs of the pool of genomic loci in the DNA of the cancer cells in the test sample from the subject with the shrunken centroid values derived from the CNVs of a reference set of samples of BRCA-like mutated cancer cells and of control samples of BRCA non-mutated cancer cells, and optionally
- (c) transmitting the result to the subject or a third party.
Dependencies are inferred from the claim text.