Prostate Cancer-Specific Alternations in ERG Gene Expression and Detection and Treatment Methods Based on Those Alterations
AssigneeThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
InventorsShiv Srivastava, Albert Dobi, Taduru Sreenath, Gyorgy Petrovics, Chen Sun
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Abstract
The disclosure describes alterations in ERG gene expression. ERG isoforms and promoter sequence of the ERG gene that are involved in, or associated with, prostate cancer are provided. The disclosure further provides therapeutic compositions and methods of detecting, diagnosing, prognosing, and treating prostate cancer, including biomarkers for detecting the expression of two or more of the following genes: PSA/KLK3, PMEPA1, NKX3.1, ODC1, AMD1, and ERG.
Claims24
A method of detecting prostate cancer in a biological sample comprising:
- (a) combining the biological sample with at least a first and a second oligonucleotide primer under hybridizing conditions, wherein the first oligonucleotide primer contains a sequence that hybridizes to a first sequence in a target sequence from ERG8, EPC1, or EPC2 and the second oligonucleotide primer contains a sequence that hybridizes to a second sequence in a nucleic acid strand complementary to the target sequence, wherein the first sequence does not overlap with the second sequence;
- (b) amplifying a plurality of amplification products when the target sequence is present in the biological sample by adding at least one polymerase activity to the biological sample containing the first and second oligonucleotide primers;
- (c) immobilizing the plurality of amplification products;
- (d) combining an oligonucleotide probe with the immobilized plurality of amplification products to thereby permit the probe to hybridize to at least one immobilized amplification product;
- and
- (e) detecting whether a signal results from hybridization between the oligonucleotide probe and at least one amplification product, wherein detection of the signal indicates the expression of ERG8, EPC1, or EPC2 and the presence of prostate cancer in the biological sample.
An isolated nucleic acid encoding the amino acid sequence set forth in SEQ ID NO:
- 4 (EPC1), or the complement thereof.
An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 4 (EPC1).
An isolated nucleic acid encoding the amino acid sequence set forth in SEQ ID NO:
- 6 (EPC2), or the complement thereof.
An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 6 (EPC2).
17-28. (canceled)
An isolated nucleic acid, comprising at least about 15 contiguous nucleotides of nucleotides 788 to 1019 of SEQ ID NO:
- 3, wherein the nucleic acid is capable of hybridizing to SEQ ID NO:
- 3, or the complement thereof, under conditions of high stringency but not to ERG1, ERG2, ERG3, ERG4, ERG5, ERG6, ERG7, ERG8, ERG9, EPC2, or TMPRSS2.
An isolated nucleic acid, comprising at least about 15 contiguous nucleotides of nucleotides 127 to 807 of SEQ ID NO:
- 5, wherein the nucleic acid is capable of hybridizing to SEQ ID NO:
- 5, or the complement thereof, under conditions of high stringency but not to ERG1, ERG2, ERG3, ERG4, ERG5, ERG6, ERG7, ERG8, ERG9, EPC1, or TMPRSS2.
35-45. (canceled)
Dependencies are inferred from the claim text.