DISTINGUISHING PCA3 MESSENGER RNA SPECIES IN BENIGN AND MALIGNANT PROSTATE TISSUES
First Claim
1. A method of determining the malignancy status of prostate cells contained in a sample undergoing testing, said method comprising determining from PCA3 RNAs from prostate cells contained in said sample or from cDNAs derived therefrom, whether said PCA3 RNAs or cDNAs comprise or lack an additional sequence between PCA3 exon 3 and PCA3 exon 4a, said additional sequence consisting essentially of nucleotides 27 to 254 of SEQ ID NO:
- 1,wherein a presence or level of a PCA3 nucleic acid molecule comprising said additional sequence is indicative of a non-malignant status of said prostate cells, andwherein a presence or level of a PCA3 nucleic acid molecule which lacks said additional sequence and comprises nucleotide positions 26 and 27 of SEQ ID NO;
2, which define the PCA3 exon 3-exon 4a junction, is indicative of a malignant status of said prostate cells.
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Abstract
This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.
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Citations
18 Claims
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1. A method of determining the malignancy status of prostate cells contained in a sample undergoing testing, said method comprising determining from PCA3 RNAs from prostate cells contained in said sample or from cDNAs derived therefrom, whether said PCA3 RNAs or cDNAs comprise or lack an additional sequence between PCA3 exon 3 and PCA3 exon 4a, said additional sequence consisting essentially of nucleotides 27 to 254 of SEQ ID NO:
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wherein a presence or level of a PCA3 nucleic acid molecule comprising said additional sequence is indicative of a non-malignant status of said prostate cells, and wherein a presence or level of a PCA3 nucleic acid molecule which lacks said additional sequence and comprises nucleotide positions 26 and 27 of SEQ ID NO;
2, which define the PCA3 exon 3-exon 4a junction, is indicative of a malignant status of said prostate cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A kit for determining whether PCA3 RNA contained in a patient sample, comprises or lacks an additional sequence between PCA3 exon 3 and PCA3 exon 4a, said additional sequence consisting essentially of nucleotides 27 to 254 of SEQ ID NO:
- 1, said kit comprising at least two oligonucleotides which bind to a PCA3 nucleic acid comprising a sequence selected from the group consisting of;
i) the PCA3 exon 3-exon 4a junction defined by nucleotide positions 26 and 255 of SEQ ID NO;
1, and by nucleotide positions 26 and 27 of SEQ ID NO;
2;ii) the PCA3 exon 3-intron 3 junction defined by nucleotide positions 26 and 27 of SEQ ID NO;
1; andiii) the PCA3 intron 3-exon 4a junction defined by nucleotide positions 254 and 255 of SEQ ID NO;
1,wherein a presence or level of a PCA3 nucleic acid molecule comprising said additional sequence is indicative of a non-malignant status of said prostate cells, and wherein a presence or level of a PCA3 nucleic acid molecule which lacks said additional sequence and comprises nucleotide positions 26 and 27 of SEQ ID NO;
2, which define the PCA3 exon 3-exon 4a junction, is indicative of a malignant status of said prostate cells.
- 1, said kit comprising at least two oligonucleotides which bind to a PCA3 nucleic acid comprising a sequence selected from the group consisting of;
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18. A method of distinguishing differentially expressed PCA3 nucleic acids that indicate the malignancy status of prostate cells contained in a sample undergoing testing, said method comprising:
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(a) performing a nucleic acid amplification reaction using RNAs obtained from prostate cells contained in said sample as templates with a pair of oligonucleotides that amplify PCA3 nucleic acid sequences across nucleotide positions 26 and 255 of SEQ ID NO;
1, which respectively define the PCA3 exon 3-intron 3 and intron 3-exon 4a junctions, and nucleotide positions 26 and 27 of SEQ ID NO;
2, which define the PCA3 exon 3-exon 4a junction, yielding first and second amplification products, wherein said pair of oligonucleotides comprises;(i) a first oligonucleotide which binds to, or upstream of, nucleotide position 26 of SEQ ID NO;
1, and(ii) a second oligonucleotide which binds to, or downstream of, nucleotide position 255 of SEQ ID NO;
1,wherein said first amplification product results from an amplification of a first PCA3 RNA that comprises portions of exon 3 and exon 4a sequences and an additional sequence between PCA3 exon 3 and PCA3 exon 4a, said additional sequence consisting essentially of nucleotides 27 to 254 of SEQ ID NO;
1, andwherein said second amplification product results from an amplification of a second PCA3 RNA that comprises portions of exon 3 and exon 4a sequences with PCA3 exon 3 joined to PCA3 exon 4a without including said additional sequence; and (b) detecting one of said first and second amplification products independent of the other, thereby distinguishing differentially expressed PCA3 nucleic acids that indicate the malignancy status of prostate cells contained in said sample.
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Specification