Methods of detecting, diagnosing and treating cancer and identifying neoplastic progression
OwnerBogdan Czerniak, Dennis Johnstoninventors
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Abstract
Disclosed are methods, compositions and apparatus useful in the detection, monitoring and treatment of the progression of neoplasia and preneoplastic conditions with special emphasis on the chromosomal changes related to the development and progression of urothelial neoplasia. Chromosomal changes, including LOH, at the disclosed loci demonstrate a statistically significant relation to the progression of disease state in urothelial neoplasia.
Claims95
A method of detecting a cell with a neoplastic or preneoplastic phenotype, comprising testing a sample comprising said cell for the presence of LOH (loss of heterozygosity) at one or more loci on one or more chromosomes, wherein said chromosomes are selected from a group consisting of chromosome 1, chromosome 2, chromosome 3, chromosome 4, chromosome 5, chromosome 6, chromosome 7, chromosome 8, chromosome 9, chromosome 10, chromosome 11, chromosome 12, chromosome 13, chromosome 14, chromosome 15, chromosome 16, chromosome 17, chromosome 18, chromosome 19, chromosome 20, chromosome 21 and chromosome 22, wherein an LOH at said one or more of loci is indicative of a neoplastic or preneoplastic phenotype.
A method of detecting urothelial neoplasia comprising the step of testing one or more samples from an individual for the presence of LOH at one or more loci on one or more chromosomes, wherein said chromosomes are selected from a group consisting of chromosome 1, chromosome 2, chromosome 3, chromosome 4, chromosome 5, chromosome 6, chromosome 7, chromosome 8, chromosome 9, chromosome 10, chromosome 11, chromosome 12, chromosome 13, chromosome 14, chromosome 15, chromosome 16, chromosome 17, chromosome 18, chromosome 19, chromosome 20, chromosome 21 and chromosome 22, wherein the presence of LOH at one or more of said loci is indicative of the presence of bladder cancer in said individual.
A DNA array for use in the detection of a neoplasia or preneoplastic phenotype, said DNA array comprising DNA probes, said DNA probes selected to detect LOH at one or more loci on chromosomes, wherein said chromosomes are selected from a group consisting of chromosome 1, chromosome 2, chromosome 3, chromosome 4, chromosome 5, chromosome 6, chromosome 7, chromosome 8, chromosome 9, chromosome 10, chromosome 11, chromosome 12, chromosome 13, chromosome 14, chromosome 15, chromosome 16, chromosome 17, chromosome 18, chromosome 19, chromosome 20, chromosome 21 and chromosome 22, wherein an LOH at one or more of said loci is indicative of a neoplastic or preneoplastic phenotype.
A method of detecting occult preclinical or premicroscopic stages of urothelial neoplasia, comprising:
- a) obtaining a urine sample;
- b) isolating bladder cells from said sample;
- and
- c) testing said bladder cells for allelic loss at one or more loci associated with the development of urothelial neoplasia;
- wherein said loci are selected from the group consisting of D1S243, D1S1608, D1S548, D1S198, D1S221, APOA2, TPO, D2S1240, D2S378, D2S114, D2S294, D2S159, D3S1298, D3S1278, D3S1303, D3S1541, ACPP, D3S1512, D3S1246, D3S1754, D3S1262 and D3S1661 D4S405, D4S828, D4S1548, D4S1597, D4S1607, D4S408, D5S428, APCII, D5S346, D5S421, MCC, D5S659, D5S404, D5S2055, D5S818, IRF1, CFS1R, D5S1465, EDN1, D6S251, D6S262, D6S290, D6S1027, D7S526, D8S136, D8S133, D8S137, D8S259, ANKI, D8S285, D8S553, D9S286, D9S156, D9S304, D9S273, D9S166, D9S252, D9S287, D9S180, D9S66, D10S1214, D10S213, D10S606, D10S215, D10S1242, D10S190, D10S217, D11S922, D11S569, D11S2368, D11S1301, D11S937, D11S931, D11S897, D11S924, D11S1284, D11S933, D11S910, D12S397, D13S221, D13S171, D13S291, RB1, RB1.2, D13S164, D13S268, D13S271, D13S154, D14S290, D14S68, D15S207, D15S107, D16S513, D16S500, D16S541, D16S415, D16S512, D16S505, D16S520, D17S578, D17S849, TP53, D17S960, D17S786, D17S799, D17S947, D17S579, D17S933, D17S932, D17S934, D17S943, D17S807, D17S784, D18S452, D18S66, D18S68, D19S406, D19S714, D19S225, D21S212, D22S264, D22S446, D22S280 and D22S423.
A method of detecting urothelial neoplasia, comprising:
- a) obtaining a urine sample;
- b) isolating bladder cells from said sample;
- and
- c) testing said bladder cells for allelic loss at one or more loci associated with the development of urothelial neoplasia;
- wherein said loci are selected from the group consisting D1S243, D1S1608, D1S548, D1S198, D1S221, APOA2, TPO, D2S1240, D2S378, D2S114, D2S294, D2S159, D3S1298, D3S1278, D3S1303, D3S1541, ACPP, D3S1512, D3S1246, D3S1754, D3S1262 and D3S1661 D4S405, D4S828, D4S1548, D4S1597, D4S1607, D4S408, D5S428, APCII, D5S346, D5S421, MCC, D5S659, D5S404, D5S2055, D5S818, IRF1, CFS1R, D5S1465, EDN1, D6S251, D6S262, D6S290, D6S1027, D7S526, D8S136, D8S133, D8S137, D8S259, ANKI, D8S285, D8S553, D9S286, D9S156, D9S304, D9S273, D9S166, D9S252, D9S287, D9S180, D9S66, D10S1214, D10S213, D10S606, D10S215, D10S1242, D10S190, D10S217, D11S922, D11S569, D11S2368, D11S1301, D11S937, D11S931, D11S897, D11S924, D11S1284, D11S933, D11S910, D12S397, D13S221, D13S171, D13S291, RB1, RB1.2, D13S164, D13S268, D13S271, D13S154, D14S290, D14S68, D15S207, D15S107, D16S513, D16S500, D16S541, D16S415, D16S512, D16S505, D16S520, D17S578, D17S849, TP53, D17S960, D17S786, D17S799, D17S947, D17S579, D17S933, D17S932, D17S934, D17S943, D17S807, D17S784, D18S452, D18S66, D18S68, D19S406, D19S714, D19S225, D21S212, D22S264, D22S446, D22S280 and D22S423.
Dependencies are inferred from the claim text.