Molecular markers
Abstract
The present invention relates to genetic sequences exhibiting differential expression patterns in cancer tissue relative to normal tissue. The identification of such sequences permits their use as molecular markers for cancer, as early indicators of cancer progression and/or as predictive markers for a propensity or likelihood of a cancer to develop. The present invention relates particularly to genetic sequences exhibiting expression patterns up-regulated in cervical cells or associated with pre-, early- or late-onset cervical cancer relative to normal cervical cells, such sequences serving as biomarkers. The biomarkers of the present invention provide targets for the development of therapeutic protocols for the treatment or prophylaxis of cervical or related cancer. Such therapeutic protocols are directed to inhibiting expression of the marker or inhibiting the expression product of the marker. The invention is further directed to a method for identifying molecular markers which are useful indicators of cervical cancer and/or its progression.
Claims
exact text as granted — not AI-modified1 - 43 . (canceled)
44 . A method for distinguishing between normal tissue and cervical cancer tissue comprising detecting differential expression of at least one polynucleotide selected from the group consisting of G30CA(SEQ ID NO:5), G30CB(SEQ ID NO:6), G30CD(SEQ ID NO:8), G30CE(SEQ ID NO:9), G30CH(SEQ ID NO:10), G30CI(SEQ ID NO:11), G30CK(SEQ ID NO:12), G31C4B(SEQ ID NO:13), G31C4C(SEQ ID NO:14), G31C5C(SEQ ID NO:15), G31C5D(SEQ ID NO:16), G31C5E(SEQ ID NO:17), G31C5G(SEQ ID NO:18), G31C6B(SEQ ID NO:20), G32C2A(SEQ ID NO:21), G32C2B(SEQ ID NO:22), G32C2C(SEQ ID NO:23), G32C3A(SEQ ID NO:24), G32C3B(SEQ ID NO:25), G32C3C(SEQ ID NO:26), G32C4B(SEQ ID NO:27), G32C4D(SEQ ID NO:28), G32C5A(SEQ ID NO:29), G32C6(SEQ ID NO:30), and G32C7(SEQ ID NO:31) in cervical cancer cells relative to normal cervical epithelial cells.
45 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CA(SEQ ID NO:5).
46 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CB(SEQ ID NO:6).
47 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CD(SEQ ID NO:8).
48 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CE(SEQ ID NO:9).
49 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CH(SEQ ID NO:10).
50 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CI(SEQ ID NO:11).
51 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G30CK(SEQ ID NO:12).
52 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C4B(SEQ ID NO:13).
53 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C4C(SEQ ID NO:14).
54 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C5C(SEQ ID NO:15).
55 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C5D(SEQ ID NO:16).
56 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C5E(SEQ ID NO:17).
57 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C5G(SEQ ID NO:18).
58 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G31C6B(SEQ ID NO:20).
59 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C2A(SEQ ID NO:21).
60 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C2B(SEQ ID NO:22).
61 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C2C(SEQ ID NO:23).
62 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C3A(SEQ ID NO:24).
63 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C3B(SEQ ID NO:25).
64 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C3C(SEQ ID NO:26).
65 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C4B(SEQ ID NO:27).
66 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C4D(SEQ ID NO:28).
67 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C5A(SEQ ID NO:29).
68 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C6(SEQ ID NO:30).
69 . A method according to claim 44 wherein the DNA molecules comprise the sequence of G32C7(SEQ ID NO:31).
70 . A method according to claim 44 or claim 65 wherein the DNA molecules encode an NADH dehydrogenase.
71 . An isolated polynucleotide comprising a sequence of nucleotides selected from the group consisting of G30CE(SEQ ID NO:9), G30CK(SEQ ID NO:12), G31C4C(SEQ ID NO:14), G31C5C(SEQ ID NO:15), G31C5D(SEQ ID NO:16), G31C5G(SEQ ID NO:18), G32C2A(SEQ ID NO:21), G32C3C(SEQ ID NO:26), G32C4D(SEQ ID NO:28), and G32C5A(SEQ ID NO:29); wherein said polynucleotide is expressed differentially in cervical cancer cells relative to matched normal cervical epithelial cells in a mammal.
72 . The method of claim 44 wherein the detection comprises RNA-RNA in situ hybridisation
73 . The method according to claim 44 wherein the detection comprises cDNA microarray analysis.
74 . The method according to claim 44 wherein the detection comprises Northern blot analysis.
75 . The method according to claim 44 wherein the detection comprises reverse Northern blot analysis.
76 . The method of claim 44 , wherein the detection comprises detection of a translation product.
77 . The method of claim 44 , wherein the detection comprises:
isolating total RNA from said cervical cancer tissue and corresponding tissue from a normal individual; generating complementary DNA molecules using reverse transcriptase-polymerase chain reaction (RT-PCR), wherein said complementary DNA molecules comprise at least one polynucleotide sequence selected from the group consisting of G30CA(SEQ ID NO:5), G30CB(SEQ ID NO:6), G30CD(SEQ ID NO:8), G30CE(SEQ ID NO:9), G30CH(SEQ ID NO:10), G30CI(SEQ ID NO:11), G30CK(SEQ ID NO:12), G31C4B(SEQ ID NO:13), G31C4C(SEQ ID NO:14), G31C5C(SEQ ID NO:15), G31C5D(SEQ ID NO:16), G31C5E(SEQ ID NO:17), G31C5G(SEQ ID NO:18), G31C6B(SEQ ID NO:20), G32C2A(SEQ ID NO:21), G32C2B(SEQ ID NO:22), G32C2C(SEQ ID NO:23), G32C3A(SEQ ID NO:24), G32C3B(SEQ ID NO:25), G32C3C(SEQ ID NO:26), G32C4B(SEQ ID NO:27), G32C4D(SEQ ID NO:28), G32C5A(SEQ ID NO:29), G32C6(SEQ ID NO:30), and G32C7(SEQ ID NO:31); subjecting said complementary DNA molecules to separation means such that the relative presence or absence of complementary DNA molecules can be detected from cervical cancer tissues relative to normal tissue; and detecting differential expression of said at least one polynucleotide sequence.
78 . A method according to claim 77 wherein a primer used in said RT-PCR is as set forth in SEQ ID NO:2.
79 . A method according to claim 77 wherein a primer used in said RT-PCR is as set forth in SEQ ID NO:2.
78 . A method according to claim 77 wherein a primer used in RT-PCR is as set forth in SEQ ID NO:3.
79 . A method according to claim 77 wherein primer used in RT-PCR is as set forth in SEQ ID NO:4.Cited by (0)
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