Methods of diagnosing or treating prostate cancer using the ERG gene, alone or in combination with other over or under expressed genes in prostate cancer
View Patent ↗The present invention relates to oncogenes or tumor suppressor genes, as well as other genes, involved in prostate cancer and their expression products, as well as derivatives and analogs thereof. Provided are therapeutic compositions and methods of detecting and treating cancer, including prostate and other related cancers. Also provided are methods of diagnosing and/or prognosing prostate cancer by determining the expression level of at least one prostate cancer-cell-specific gene, including, for example, the ERG gene or the LTF gene alone, or in combination with at least one of the AMACR gene and the DD3 gene.
1. A method of identifying and treating prostate cancer with a Gleason score of 6 to 9 in a subject, the method comprising:
(a) measuring the RNA expression levels of genes in a urine sample from the subject, wherein the genes consist of a three-gene prostate cancer-cell-specific gene expression signature, wherein one of the three genes in the signature is an ERG gene;
(b) comparing the RNA expression level of the ERG gene measured in step (a) to an RNA expression level of an ERG gene in a control sample, wherein the control sample is a urine sample from a subject without prostate cancer; and
(c) determining that the RNA expression level of the ERG gene measured in step (a) is at least two times greater than the RNA expression level of the ERG gene in the control sample, thereby identifying the subject as having a prostate cancer with a Gleason Score of 6 to 9; and
(d) administering to the subject a therapeutic treatment suitable for amelioration of the prostate cancer in the subject.
2. The method of claim 1 , wherein the expression levels are measure by nucleic acid amplification.
3. The method of claim 1 , wherein the ERG gene comprises SEQ ID NO: 1, or wherein the ERG gene comprises SEQ ID NO: 2.
4. The method of claim 1 , wherein:
the three-gene prostate cancer-cell-specific gene expression signature of step (a) includes the AMACR gene;
step (b) includes comparing the RNA expression level of the AMACR gene measured in step (a) to the RNA expression level of the AMACR gene in a control sample, wherein the control sample is a urine sample from a subject without prostate cancer; and
step (c) includes determining that the RNA expression level of the AMACR gene measured in step (a) is at least two times greater than the RNA expression level of the AMACR gene in the control sample.
5. The method of claim 4 , wherein the AMACR gene comprises SEQ ID NO: 3.
6. The method of claim 1 , wherein:
the three-gene prostate cancer-cell-specific gene expression signature of step (a) includes the PCA3 gene;
step (b) includes comparing the RNA expression level of the PCA3 gene measured in step (a) to the RNA expression level of the PCA3 gene in a control sample,
wherein the control sample is a urine sample from a subject without prostate cancer; and
step (c) includes determining that the RNA expression level of the PCA3 gene measured in step (a) is at least two times greater than the RNA expression level of the PCA3 gene in the control sample.
7. The method of claim 6 , wherein the PCA3 gene comprises SEQ ID NO: 4.
8. A method of treating a prostate cancer having a Gleason Score of 6 to 9 in a subject, the method comprising administering to the subject a therapeutic treatment suitable for amelioration of the prostate cancer in the subject, wherein prior to the administration:
(a) the RNA expression levels of genes in a urine sample from the subject, wherein the genes consist of a three-gene prostate cancer-cell-specific gene expression signature, wherein one of the three genes in the signature is an ERG gene, was measured;
(b) the RNA expression level of the ERG gene measured in step (a) was compared to an RNA expression level of an ERG gene in a control sample, wherein the control sample is a urine sample from a subject without prostate cancer; and
(c) the RNA expression level of the ERG gene measured in step (a) was determined to be least two times greater than the RNA expression level of the ERG gene in the control sample, thereby identifying the subject as having a prostate cancer with a Gleason Score of 6 to 9.
9. The method of claim 8 , wherein the ERG gene comprises SEQ ID NO: 1 or wherein the ERG gene comprises SEQ ID NO: 2.