Methods and compositions for the prediction, diagnosis, prognosis, prevention and treatment of malignant neoplasma
First Claim
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1. A method for the prediction, diagnosis or prognosis of malignant neoplasia by the detection of at least 2 markers characterized in that the markers are genes and fragments thereof or genomic nucleic acid sequences that are located on one chromosomal region which is altered in malignant neoplasia.
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Abstract
The invention provides novel compositions, methods and uses, for the prediction, diagnosis, prognosis, prevention and treatment of malignant neoplasia and breast cancer in particular. Genes that are differentially expressed in breast tissue of breast cancer patients versus those of normal people are disclosed.
171 Citations
27 Claims
- 1. A method for the prediction, diagnosis or prognosis of malignant neoplasia by the detection of at least 2 markers characterized in that the markers are genes and fragments thereof or genomic nucleic acid sequences that are located on one chromosomal region which is altered in malignant neoplasia.
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2. A method for the prediction, diagnosis or prognosis of malignant neoplasia by the detection of at least 2 markers characterized in that the markers are:
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a) genes that are located on one or more chromosomal region(s) which is/are altered in malignant neoplasia; and
b) i) receptor and ligand;
orii) members of the same signal transduction pathway;
oriii) members of synergistic signal transduction pathways;
oriv) members of antagonistic signal transduction pathways;
orv) transcription factor and transcription factor binding site.
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- 8. A method for the prediction, diagnosis or prognosis of malignant neoplasia by the detection of at least one marker whereby the marker is a VNTR, SNP, RFLP or STS characterized in that the marker is located on one chromosomal region which is altered in malignant neoplasia due to amplification and the marker is detected in a cancerous and a non-cancerous tissue or biological sample of the same individual.
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11. A method for the prediction, diagnosis or prognosis of malignant neoplasia by the detection of at least one marker characterized in that the marker is selected from:
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a) a polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
2 to 6, 8, 9, 11 to 16, 18, 19, 21 to 26 or 53 to 75;
b) a polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) and encodes a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 c) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (c) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 d) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (d) e) a purified polypeptide encoded by a polynucleotide or polynucleotide analog sequence specified in (a) to (e) f) a purified polypeptide comprising at least one of the sequences of SEQ ID NO;
28 to 32, 34, 35, 37 to 42, 44, 45, 47 to 52 or 76 to 98;
are detected.
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12. A method for the prediction, diagnosis or prognosis of malignant neoplasia by the detection of at least 2 markers characterized in that at least 2 markers are selected from:
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a) a polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
1 to 26 or 53 to 75;
b) a polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) and encodes a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 c) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 d) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c) e) a purified polypeptide encoded by a polynucleotide sequence or polynucleotide analog specified in (a) to (d) f) a purified polypeptide comprising at least one of the sequences of SEQ ID NO;
27 to 52 or 76 to 98are detected.
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15. A composition for the prediction, diagnosis or prognosis of malignant neoplasia comprising:
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a) a detection agent for;
i) any polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
2 to 6, 8, 9, 11 to 16, 18, 19, 21 to 26 or 53 to 75;
ii) any polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 iii) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 iv) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c) v) a polypeptide encoded by a polynucleotide or polynucleotide analog sequence specified in (a) to (d);
vi) a polypeptide comprising at least one of the sequences of SEQ ID NO;
28 to 32, 34, 35, 37 to 42, 44, 45, 47 to 52 or 76 to 98. orb) at least 2 detection agents for at least 2 markers selected from;
i) any polynucleotide comprising at least one of the sequences of SEQ ID NO;
1 to 26 or 53 to 75;
ii) any polynucleotide which hybridizes under stringent conditions to a polynucleotide specified in (a) encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 iii) a polynucleotide the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 iv) a polynucleotide which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c) v) a polypeptide encoded by a polynucleotide sequence specified in (a) to (d);
vi) a polypeptide comprising at least one of the sequences of SEQ ID NO;
27 to 52 or 76 to 98.
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16. An array comprising a plurality of polynucleotides or polynucleotide analogs wherein each of the polynucleotides is selected from:
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a) a polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
1 to 26 or 53 to 75;
b) a polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 c) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 d) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c) attached to a solid support.
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17. A method of screening for agents which regulate the activity of a polypeptide encoded by a polynucleotide or polynucleotide analog selected from the group consisting of:
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a) a polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
2 to 6, 8, 9, 11 to 16, 18, 19, 21 to 26 or 53 to 75;
b) a polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 c) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 d) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c);
comprising the steps of;
i) contacting a test compound with at least one polypeptide encoded by a polynucleotide specified in (a) to (d); and
ii) detecting binding of the test compound to the polypeptide, wherein a test compound which binds to the polypeptide is identified as a potential therapeutic agent for modulating the activity of the polypeptide in order to prevent of treat malignant neoplasia. - View Dependent Claims (20, 21, 22, 23, 24)
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18. A method of screening for agents which regulate the activity of a polypeptide encoded by a polynucleotide or polynucleotide analog selected from the group consisting of:
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a) a polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
2 to 6, 8, 9, 11 to 16, 18, 19, 21 to 26 or 53 to 75;
b) a polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 c) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 d) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c) comprising the steps of;
i) contacting a test compound with at least one polypeptide encoded by a polynucleotide specified in (a) to (d); and
ii) detecting the activity of the polypeptide as specified for the respective sequence in Table 2 or 3, wherein a test compound which increases the activity is identified as a potential preventive or therapeutic agent for increasing the polypeptide acitivity in malignant neoplasia, and wherein a test compound which decreases the activity of the polypeptide is identified as a potential therapeutic agent for decreasing the polypeptide activity in malignant neoplasia.
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19. A method of screening for agents which regulate the activity of a polynucleotide or polynucleotide analog selected from group consisting of;
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a) a polynucleotide or polynucleotide analog comprising at least one of the sequences of SEQ ID NO;
2 to 6, 8, 9, 11 to 16, 18, 19, 21 to 26 or 53 to 75;
b) a polynucleotide or polynucleotide analog which hybridizes under stringent conditions to a polynucleotide specified in (a) encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 c) a polynucleotide or polynucleotide analog the sequence of which deviates from the polynucleotide specified in (a) and (b) due to the generation of the genetic code encoding a polypeptide exhibiting the same biological function as specified for the respective sequence in Table 2 or 3 d) a polynucleotide or polynucleotide analog which represents a specific fragment, derivative or allelic variation of a polynucleotide sequence specified in (a) to (c) comprising the steps of;
i) contacting a test compound with at least one polynucleotide or polynucleotide analog specified in (a) to (d), and ii) detecting binding of the test compound to the polynucleotide, wherein a test compound which binds to the polynucleotide is identified as a potential preventive or therapeutic agent for regulating the activity of the polynucleotide in malignant neoplasia.
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25. A computer-readable medium comprising:
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a) at least one digitally encoded value representing a level of expression of at least one polynucleotide sequence of SEQ ID NO;
2 to 6, 8, 9, 11 to 16, 18, 19, 21 to 26 or 53 to 75b) al least 2 digitally encoded values representing the levels of expression of at least 2 polynucleotide sequences selected from SEQ ID NO;
1 to 26 or 53 to 75in a cell from the a subject at risk for or having malignant neoplasia.
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26. A method for the detection of chromosomal alterations characterized in that the relative abundance of individual mRNAs, encoded by genes, located in altered chromosomal regions is detected.
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27. A method for the detection of chromosomal alterations characterized in that the copy number of one or more chromosomal region(s) is detected by quantitative PCR.
Specification