Abstract: The present invention relates to methods of determining the presence or absence of certain cancers in a human individual, as well as to related methods to determine the response to therapy against certain cancers in a human individual, in particular ovarian cancer in a woman. Such methods are based on the detection-from (eg cell-free) DNA of said human individual—of one or more methylated (or un-methylated) CpGs being associated with differentially methylated regions (DMRs) of the present invention; such as methylation (or un-methylation) at one or more or all of certain CpGs being associated with such DMRs. Accordingly, such methods have diagnostic, prognostic and/or predictive utility for detecting or managing certain cancers in women or men, in particular ovarian cancer in women.

Abstract: The present invention relates to assays for predicting the presence, absence or development of CIN3 and/or cancer, particularly cervical or endometrial cancer, most preferably cervical cancer, in an individual, particularly cervical and endometrial cancer, by determining the methylation status of certain CpGs in a population of DNA molecules in a sample which has been taken from the individual, deriving an index value based on the methylation status of the certain CpGs, and predicting the presence, absence or development of CIN3 and/or cancer, particularly cervical or endometrial cancer, most preferably cervical cancer, in the individual based on the cancer index value.

Abstract: The present invention relates to assays for predicting the presence, absence or development of breast cancer in an individual, by determining the methyl ati on status of certain CpGs in a population of DNA molecules in a sample which has been taken from the individual, deriving an index value based on the methylation status of the certain CpGs, and predicting the presence, absence or development of breast cancer in the individual based on the breast cancer index value. The invention further relates to a method of treating and/or preventing breast cancer in an individual, the method comprising assessing the presence, absence or development of breast cancer in an individual by performing the assays of the invention, followed by administering one or more therapeutic or preventative treatments or measures to the individual based on the assessment.

Abstract: The invention relates to a method of determining whether a subject is at an increased risk of developing or having ovarian cancer or being a carrier of a germline BRCA1 and/or BRCA2 mutation. The method may comprise determining whether the percentage contribution of lactic acid-producing bacteria to the bacterial load of a sample obtained from the lower genital tract of the subject is more or less than a percentage threshold level. The subject is at increased risk if the percentage contribution of lactic acid-producing bacteria to the bacterial load of the sample is less than the percentage threshold level. Alternatively, the method may comprise determining the pH of a sample obtained from the lower genital tract of the subject. The subject is at increased risk if the pH is higher than a pH threshold level.

Abstract: The present invention relates to assays for predicting the presence or development of breast cancer in an individual, by determining the methylation status of certain CpGs in DNA from the individual, deriving an index value based on the methylation status of the certain CpGs, and predicting the development of breast cancer in the individual based on the breast cancer index value.

Abstract: The present invention relates to methods of identifying the presence of DNA from one or more metastatic breast cancer (mBC) cells in a sample from an individual. The invention also relates to methods of diagnosing metastatic breast cancer (mBC) by identifying the presence of mBC cell DNA in a sample from an individual. The invention also relates to methods of identifying a breast cancer patient as having a poor disease prognosis by identifying the presence of DNA from one or more mBC cells in a sample from an individual. The invention additionally relates to methods of identifying in DNA from an individual the presence of a methylation signature associated with mBC by identifying the presence of DNA from one or more mBC cells in a sample from an individual.

Abstract: The present invention relates to methods of determining the presence or absence of certain cancers in a human individual, as well as to related methods to determine the response to therapy against certain cancers in a human individual, in particular ovarian cancer in a woman. Such methods are based on the detection-from (eg cell-free) DNA of said human individual—of one or more methylated (or un-methylated) CpGs being associated with differentially methylated regions (DMRs) of the present invention; such as methylation (or un-methylation) at one or more or all of certain CpGs being associated with such DMRs. Accordingly, such methods have diagnostic, prognostic and/or predictive utility for detecting or managing certain cancers in women or men, in particular ovarian cancer in women.

Abstract: The present invention relates to methods of determining the presence or absence of an ovarian cancer in a woman, as well as to related methods to determine the response to therapy against ovarian cancer in a woman. Such methods are based on the detection—from cell-free DNA of said woman—of one or more methylated (or un-methylated) CpGs being associated with differentially methylated regions (DMRs) of the present invention;such as methylation (or un-methylation) at one or more or all of certain CpGs being associated with such DMRs. Accordingly, such methods have diagnostic, prognostic and/or predictive utility for detectingor managing ovarian cancer in women.

Abstract: The present invention relates to methods and means for detecting cancer or of predicting a patient developing cancer or of determining the rate of progression of cancer in a patient suffering from cancer, comprising determining RANKL activity and/or the amount of OPG in a sample of said patient.

Abstract: The present invention relates to methods and means for detecting cancer or of predicting a patient developing cancer or of determining the rate of progression of cancer in a patient suffering from cancer, comprising determining RANKL activity and/or the amount of OPG in a sample of said patient.

Abstract: In particular aspects, stem-cell polycomb group (PcG) targets are more likely to have cancer-specific promoter DNA methylation than non-targets, indicating a stem-cell origin of cancer, where reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and predisposition to subsequent malignant transformation. Exemplary aspects provide methods for identifying preferred DNA methylation markers for a cellular proliferative disorder and/or cancer and markers for developmental lineages and/or stages, based on identifying PcG protein or PcG repressive complex genomic target loci within a precursor cell (e.g., stem or progenitor cell) population, and determining, in cells of the proliferative disorder and/or cancer or cell of the particular developmental lineages and/or stages, a characteristic methylation status of the PcG target loci. Additional aspects provide methods for validating and/or monitoring a precursor cell (e.g., stem cell) population.

Abstract: Particular embodiments provide novel and clinically useful DNA methylation predictors of hormone receptor status, and predictors of response to endocrine (e.g., hormonal) and non-endocrine breast cancer therapy. The ESR1 gene, encoding the estrogen receptor (ER) alpha proved to be the preferred predictor of progesterone receptor (PR) status, while methylation of the PGR gene, encoding PR, was the preferred predictor of ER status. ESR1 methylation outperformed hormone receptor status as a predictor of clinical response in patients treated with antiestroges (e.g., tamoxifen), while promoter methylation of the CYP1B1 gene, encoding a tamoxifen and estradiol metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and non-treated patients. High levels of promoter methylation of the ARH1 gene, encoding a RAS-related small G-protein, were shown to be preferred predictors of better survival in patients who had not received tamoxifen therapy.

Abstract: In particular aspects, stem-cell polycomb group (PcG) targets are more likely to have cancer-specific promoter DNA methylation than non-targets, indicating a stem-cell origin of cancer, where reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and predisposition to subsequent malignant transformation. Exemplary aspects provide methods for identifying preferred DNA methylation markers for a cellular proliferative disorder and/or cancer and markers for developmental lineages and/or stages, based on identifying PcG protein or PcG repressive complex genomic target loci within a precursor cell (e.g., stem or progenitor cell) population, and determining, in cells of the proliferative disorder and/or cancer or cell of the particular developmental lineages and/or stages, a characteristic methylation status of the PcG target loci. Additional aspects provide methods for validating and/or monitoring a precursor cell (e.g., stem cell) population.

Abstract: The present invention relates to prognostic and diagnostic markers for cell proliferative disorders of the breast tissues. The present invention therefore provides methods and nucleic acids for the analysis of biological samples for features associated with the development of breast cell proliferative disorders. Furthermore, the invention provides for prognosis of treatment effects relating to drug therapy, in particular hormonal/antihormonal therapy, chemotherapy and/or adjuvant therapy.

Abstract: Particular embodiments provide novel and clinically useful DNA methylation predictors of hormone receptor status, and predictors of response to endocrine (e.g., hormonal) and non-endocrine breast cancer therapy. The ESR1 gene, encoding the estrogen receptor (ER) alpha proved to be the preferred predictor of progesterone receptor (PR) status, while methylation of the PGR gene, encoding PR, was the preferred predictor of ER status. ESR1 methylation outperformed hormone receptor status as a predictor of clinical response in patients treated with antiestroges (e.g., tamoxifen), while promoter methylation of the CYP1B1 gene, encoding a tamoxifen and estradiol metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and non-treated patients. High levels of promoter methylation of the ARHI gene, encoding a RAS-related small G-protein, were shown to be preferred predictors of better survival in patients who had not received tamoxifen therapy.