Breast cancer biomarker signatures for invasiveness and prognosis
AssigneeThe Ohio State University
InventorsCarlo M. Croce, Stefano Volinia
Life of this patent
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Abstract
MicroRNA profiles transition from normal breast to ductal carcinoma in situ and transition to invasive ductal carcinoma (IDC) and methods of use thereof are described. Methods of diagnosis and prognosis using microRNA signatures to differentiate invasive from in situ carcinoma are described. Also described is the use of microRNA expression for predicting overall survival and time to metastasis.
Claims13
A method of diagnosing whether a subject has breast invasive ductal carcinoma (IDC) as compared to ductal carcinoma in situ (DCIS), comprising:
- a) reverse transcribing RNA from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides wherein the subject has breast IDC;
- b) hybridizing the target oligodeoxynucleotides to a microarray comprising miR-210, let-7d and miR-221 specific probe oligonucleotides to provide a hybridization profile for the test sample;
- and
- c) comparing the test sample hybridization profile to a hybridization profile generated from a control sample, wherein an increase in the expression of miR-210, let-7d and miR-221 is indicative of the subject having IDC as compared to ductal carcinoma in situ (DCIS).
A method of determining disease progression of breast invasive ductal carcinoma (IDC) in a subject as compared to ductal carcinoma in situ (DCIS), comprising:
- a) identifying the relative miR-210 expression compared to a control by:
- i) extracting a test sample of tissue from a human subject, wherein the extracting is by hypodermic needle, microdissection, or laser capture;
- and
- ii) measuring by microarray analysis the level of a miRNA/mRNA signature in the test sample of tissue from the human subject, the miRNA/mRNA signature consisting of miR-210, let-7d and miR-221;
- and,
- b) determining the disease progression as IDC in the subject if the subject has increased miR-210, let-7d and miR-221 expression compared to the control;
- or, determining no disease progression if the subject does not have increased miR-210, let-7d and miR-221 expression compared to the control.
A method for determining the likelihood of breast cancer progression in a human subject having breast cancer, comprising:
- a) determining the expression level of a signature of hsa-miR-210, hsa-let-7d and hsa-miR-221 in a sample containing breast cancer cells from the subject with breast cancer, by assaying by microarray analysis a nucleic acid sample obtained from the breast cancer cells to determine the expression level of the miRNA signature in the nucleic acid sample;
- b) comparing the expression level from step a) to a standard miRNA expression level in a control sample, and
- determining that the subject has a poor survival outcome, if there is an increase in the expression levels of miRNA signature in the nucleic acid sample, as compared to a control sample.
Dependencies are inferred from the claim text.