US2016289766A1PendingUtilityA1
Molecular prognostic signature for predicting breast cancer metastasis, and uses thereof
Est. expiryJan 31, 2027(~0.6 yrs left)· nominal 20-yr term from priority
C12Q 1/6886C12Q 2600/16C12Q 2600/118C12Q 2600/158
60
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Claims
Abstract
The present invention is based on the discovery of a unique 14-gene molecular prognostic signature that is useful for predicting breast cancer metastasis. In particular, the present invention relates to methods and reagents for detecting and profiling the expression levels of these genes, and methods of using the expression level information in predicting risk of breast cancer metastasis.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of determining risk associated with tumor metastasis in a breast cancer patient, comprising:
(a) measuring the expression level of genes comprising CENPA, PKMYT1, MELK, MYBL2, BUB1, RACGAP1, TK1, UBE2S, DC13, RFC4, PRR11, DIAPH3, ORC6L and CCNB1 in estrogen receptor-positive tumor cells of said breast cancer patient, thereby obtaining a metastasis score (MS) based upon the expression levels of said genes; and (b) determining risk of tumor metastasis for said breast cancer patient by comparing said metastasis score to at least one predefined metastasis score cut off threshold (MS threshold).
2 . The method of claim 1 , wherein in step (b), said breast cancer patient is determined to have an increased risk of tumor metastasis if its MS is higher than the predefined MS threshold.
3 . The method of claim 1 , wherein in step (b), said breast cancer patient is determined to have a decreased risk of tumor metastasis if its MS is lower than the predefined MS threshold.
4 . The method of claim 1 in which mRNA of each of said genes is reverse transcribed and amplified by the two primers associated with the corresponding gene as provided in Table 3, SEQ ID NOS:1-28.
5 . The method of claim 1 in which the expression levels of said genes are normalized against the expression level of at least one housekeeping gene, or an average of two or more housekeeping genes.
6 . The method of claim 5 , wherein the housekeeping gene is selected from the group consisting of NUP214, PPIG and SLU7.
7 . The method of claim 6 in which the mRNA of said housekeeping gene is reverse transcribed and amplified by the two primers associated with said housekeeping gene as provided in Table 3, SEQ ID NOS:29-34.
8 . The method of claim 1 in which the metastasis score (MS) is calculated by the following:
MS
=
a
0
+
∑
i
=
1
M
ai
*
Gi
where M=14, Gi=the expression level of each gene (i) of the fourteen said genes, a0=0.022, and ai corresponds to the value presented in Table 2 for each of said genes.
9 . The method of claim 1 in which the metastasis score (MS) is calculated by the following:
MS
=
a
0
+
b
*
[
∑
i
=
1
M
ai
*
Gi
]
where M=14, Gi=the standardized expression level of each gene (i) of the fourteen said genes, a0=0.022, b=−0.251 and ai corresponds to the value presented in Table 2 for each of said genes.
10 . The method of claim 1 in which the metastasis score (MS) is calculated by the following:
MS
=
a
0
+
b
*
[
∑
i
=
1
M
ai
*
Gi
]
where M=14, Gi=the expression level of each gene (i) of the fourteen said genes, a0=0.8657, b=−0.04778 and ai=1 for each of said genes.
11 . The method of claim 1 in which the metastasis score (MS) is calculated by the following:
MS
(
new
)
=
-
1
/
14
*
[
∑
i
=
1
14
Gi
]
where Gi=the expression level of each gene (i) of the fourteen said genes.
12 . The method of claim 1 in which the metastasis score (MS) is calculated by adding together the expression level of each gene of the fourteen said genes.
13 . A kit comprising reagents for detecting the expression levels of genes comprising CENPA, PKMYT1, MELK, MYBL2, BUB1, RACGAP1, TK1, UBE2S, DC13, RFC4, PRR11, DIAPH3, ORC6L and CCNB1;
an enzyme; and a buffer.
14 . The kit of claim 13 , further comprising at least one reagent for detecting the expression level of at least one housekeeping gene.
15 . The kit of claim 14 , wherein the housekeeping gene is selected from the group consisting of NUP214, PPIG and SLU7.
16 . The kit of claim 13 , wherein said reagents comprise at least one primer which comprises a nucleotide sequence selected from the group consisting of SEQ ID NOS:1-28.
17 . The kit of claim 15 , wherein said reagent comprises at least one primer which comprises a nucleotide sequence selected from the group consisting of SEQ ID NOS:29-34.
18 . A microarray comprising polynucleotides that hybridize to genes comprising CENPA, PKMYT1, MELK, MYBL2, BUB1, RACGAP1, TK1, UBE2S, DC13, RFC4, PRR11, DIAPH3, ORC6L and CCNB1.
19 . The microarray of claim 18 , further comprising one or more polynucleotides that each hybridize to a housekeeping gene.
20 . The microarray of claim 19 , wherein the housekeeping gene is selected from the group consisting of NUP214, PPIG and SLU7.Cited by (0)
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