DETECTION OF TISSUE ORIGIN OF CANCER
First Claim
1. A method for specifically identifying, in a mammal, the primary tissue origen of tumor cells in a sample, said method comprisinga) contacting a sample derived from a sample containing tumour cells from with at least one detection probe, which is a member from a collection of detection probes wherein each member of said collection comprises a recognition sequence consisting of nucleobases and affinity enhancing nucleobase analogues, and wherein the recognition sequences exhibit a combination of high melting temperatures and low self-complementarity scores, said melting temperatures being the melting temperature of the duplex between the recognition sequence and its complementary RNA sequence, said collection of detection probes being capable of specifically identifying target RNA sequences in all miRNAs of said mammal and said sample being contacted with said at least one detection probe under conditions that facilitate hybridization between said detection probe and RNA complementary to the recognition sequence of the detection probe, andb) subsequently detecting hybridization between said at least one detection probe and RNA complementary to the recogntion sequence of the detection probe.
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Accused Products
Abstract
Disclosed is a method for determining the cellular or tissue origin of tumor cells. The method entails determining the presence of at least one micro RNA (miRNA) in a sample derived from tumor tissue and based on the said determination establishing a miRNA expression profile and comparing this with pre-established miRNA expression profiles from cells, tissues or tumors. The determination uses short oligonucleotide probes comprising modified affinity-enhancing nucleobases.
38 Citations
40 Claims
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1. A method for specifically identifying, in a mammal, the primary tissue origen of tumor cells in a sample, said method comprising
a) contacting a sample derived from a sample containing tumour cells from with at least one detection probe, which is a member from a collection of detection probes wherein each member of said collection comprises a recognition sequence consisting of nucleobases and affinity enhancing nucleobase analogues, and wherein the recognition sequences exhibit a combination of high melting temperatures and low self-complementarity scores, said melting temperatures being the melting temperature of the duplex between the recognition sequence and its complementary RNA sequence, said collection of detection probes being capable of specifically identifying target RNA sequences in all miRNAs of said mammal and said sample being contacted with said at least one detection probe under conditions that facilitate hybridization between said detection probe and RNA complementary to the recognition sequence of the detection probe, and b) subsequently detecting hybridization between said at least one detection probe and RNA complementary to the recogntion sequence of the detection probe.
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2. A method for specifically identifying, in a mammal, the tissue of origin of a tumour of unknown origin, said method comprising
a) contacting a sample derived from a sample containing tumour cells of said tumour with at least one detection probe, which is a member from a collection of detection probes wherein each member of said collection comprises a recognition sequence consisting of nucleobases and affinity enhancing nucleobase analogues, and wherein the recognition sequences exhibit a combination of high melting temperatures and low self-complementarity scores, said melting temperatures being the melting temperature of the duplex between the recognition sequence and its complementary RNA sequence, said collection of detection probes being capable of specifically identifying target RNA sequences in all miRNAs of said mammal and said sample being contacted with said at least one detection probe under conditions that facilitate hybridization between said detection probe and RNA complementary to the recognition sequence of the detection probe, and b) subsequently detecting hybridization between said at least one detection probe the RNA complementary complementary to the detection probe.
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37. A method of for the treatment of cancer, said method comprising
a. isolating RNA from at least one tissue sample from a patient suffering from cancer, b. establishing an miRNA expression profile utilising RNA isolated in step a and determining at least one feature of said cancer which conforms with the miRNA expression profile, c. based on the identification feature determined in step b) diagnosing the physiological status of the cancer disease in said patient, and d. selecting and applying an appropriate form of therapy for said patient based on the said diagnosis.
Specification