Composite metastasis score with weighted coefficients for predicting breast cancer metastasis, and uses thereof
AssigneeCelera Corporation
InventorsAlice Wang, Robert J. Lagier, Charles M. Rowland
Life of this patent
Estimating the term…
Abstract
The present invention relates to a composite metastasis score (“cMS”) based on expression of a 14-gene molecular signature (referred to as a metastasis score, or “MS”) in combination with progesterone receptor (PR) expression that is useful for predicting breast cancer metastasis. In preferred embodiments, the cMS is determined by applying weighted coefficients to MS and PR. The present invention provides methods and reagents for detecting and profiling the expression levels of these genes, and methods of using the expression level information for predicting risk of breast cancer metastasis, among other embodiments.
Claims26
A method for determining risk of tumor metastasis in a human having breast cancer, comprising:
- (a) detecting the expression levels of 14 genes comprising CENPA, PKMYT1, MELK, MYBL2, BUB1, RACGAP1, TK1, UBE2S, DC13, RFC4, PRR11, DIAPH3, ORC6L and CCNB1 in a breast tumor sample from said human, and determining a metastasis score (MSu) based on the expression levels of said 14 genes;
- (b) detecting the expression level of progesterone receptor (PR) in said breast tumor sample;
- and
- (c) determining a composite metastasis score (cMSu) that indicates risk of tumor metastasis, wherein said cMSu is calculated from said MSu and said expression level of PR as follows:
- cMSu=βMS*MSu+βPR*PR
- wherein βMS is a value between 0.0006 and 0.0667, and wherein βPR is a value between −0.3614 and −0.0497.
A method for determining a composite metastasis score (cMSu) that indicates risk of tumor metastasis in a human having breast cancer, the method comprising calculating said cMSu from a metastasis score (MSu) value and a progesterone receptor (PR) value as follows:
- cMSu=βMS*MSu+βPR*PR
- wherein βMS is a value between 0.0006 and 0.0667, and wherein βPR is a value between −0.3614 and −0.0497, and wherein said MSu value represents the expression level of 14 genes comprising CENPA, PKMYT1, MELK, MYBL2, BUB1, RACGAP1, TK1, UBE2S, DC13, RFC4, PRR11, DIAPH3, ORC6L and CCNB1 in a breast tumor sample from said human, and said PR value represents the expression level of PR in said breast tumor sample.
A test kit for determining risk of breast cancer metastasis, comprising one or more containers enclosed in a package, wherein said one or more containers contain:
- a) reagents for detecting the expression levels of 14 genes comprising CENPA, PKMYT1, MELK, MYBL2, BUB1, RACGAP1, TK1, UBE2S, DC13, RFC4, PRR11, DIAPH3, ORC6L, and CCNB1, wherein said reagents comprise primers and/or probes that are optionally detectably labeled;
- b) reagents for detecting the expression level of progesterone receptor (PR), wherein said reagents comprise primers and/or probes that are optionally detectably labeled;
- c) reagents for detecting the expression level of at least one control gene, wherein said at least one control gene is optionally a housekeeping gene selected from the group consisting of NUP214, PPIG, and SLU7, and wherein said reagents comprise primers and/or probes that are optionally detectably labeled;
- and
- d) one or more components selected from the group consisting of a polymerase or other enzyme, buffer, and dNTPs;
- and wherein the following are enclosed in said package:
- i) instructions for calculating a composite metastasis score (cMS);
- ii) an insert setting forth a predefined composite metastasis score threshold cutoff value (cMS threshold);
- and
- iii) instructions for determining risk of breast cancer metastasis by comparing said cMS to said cMS threshold.
Dependencies are inferred from the claim text.