Epigenetic portraits of human breast cancers
AssigneeUniversite Libre de Bruxelles
InventorsFrançois Fuks, Sarah Dedeurwaerder, Christos Sotiriou, Christine Desmedt
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Abstract
The present invention provides new target gene regions for use in prediction, prognosis, diagnosis and therapy of breast cancer, based on the differential methylation profile of said targets in samples from subjects with breast cancer and healthy subjects.
Claims26
A method for the stratification and prognosis of breast cancer comprising the steps of:
- a) analyzing the methylation status of one or more of the genes selected from the group consisting of:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, in a sample of the subject, and
- b) comparing the methylation status of said one or more genes obtained from step a) with the methylation status of a control sample,
- wherein a difference in methylation status as detected in step b) indicates the subject has a good or a bad clinical outcome.
A method for the classification, stratification, diagnosis, prognosis or prediction of breast cancer comprising the steps of:
- a) analyzing the methylation status of all 86 CpG regions defined in Table 2 (SEQ ID Nos 1 to 86) in a sample of the subject, and
- b) comparing the methylation status of said one or more regions obtained from step a) with the methylation status of a control sample,
- wherein a difference in methylation status as detected in step b) indicates the subject has or is at risk of developing breast cancer.
A method for the stratification, prognosis or prediction of breast cancer, or for providing an indication for susceptibility to hormonotherapy comprising the steps of:
- a) analyzing the methylation status of one or more of the CpG regions defined in Table 5b (SEQ ID Nos 87 to 321) and 5c (SEQ ID Nos 322 to 499), in a sample of the subject, and
- b) comparing the methylation status of said one or more regions obtained from step a) with the methylation status of a control sample,
- wherein a difference in methylation status as detected in step b) indicates the susceptibility of the subject to respond to homotherapy.
A method of treating breast cancer by targeting one or more genes having aberrant methylation in breast cancer, defined by one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c.
A method for identifying an agent that modulates the methylation status of one or more of the genes or gene products having aberrant methylation in breast cancer, defined by one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c, comprising the steps of:
- a) contacting the candidate agent with said one or more genes, and
- b) analysing the modulation of said one or more gene by the candidate agent.
A method for establishing a reference methylation status profile comprising the steps of:
- measuring the methylation status of one or more genes having aberrant methylation in breast cancer, defined by one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c in a sample of subject.
A microarray or chip comprising one or more breast cancer specific CpG regions from one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c.
A method of treating breast cancer comprising determining the methylation status of one or more of the CpG islands from one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c in a patient sample, stratifying, prognosticating, diagnosing or predicting clinical outcome for breast cancer based upon the methylation status, selecting patients having a poor clinical outcome, and treating the patients having a poor clinical outcome.
A method of stratifying breast cancer patients comprising the steps of:
- a) analyzing the methylation status of one or more of the CpG islands from one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c, in a sample of the subject, and
- b) comparing the methylation status of said one or more genes obtained from step a) with the methylation status of a control sample selected from the group of healthy, or Basal-like, Luminal A, luminal B, HER2-plus or HER2-minus breast cancer,
- wherein a corresponding methylation status in steps a) and b) results in the identification of the type of breast cancer.
A method of selecting a breast cancer therapy comprising the steps of
- a) analyzing the methylation status of one or more of the CpG islands from one or more of the genes selected from the group comprising:
- LCK, CD3D, CD6, ICOS, CD3G, SIT1, CCL5, HCLS1, CD79B, UBASH3A, and LAX1, or CpG regions defined in Tables 2, 5b or 5c, in a sample of the subject, and
- b) comparing the methylation status of said one or more genes obtained from step a) with the methylation status of a control sample selected from the group of healthy, or Basal-like, Luminal A, luminal B, HER2-plus or HER2-minus breast cancer,
- wherein a corresponding methylation status in steps a and b results in the identification of the type of breast cancer, and
- c) identifying the appropriate treatment of the breast cancer in view of the type of cancer identified.
Dependencies are inferred from the claim text.