Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1995-08-14
1999-01-05
Myers, Carla J.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435912, 435810, 536 2431, 536 2433, 536 235, 935 8, 935 9, 935 78, C12Q 168, C12P 1934, C07H 2104
Patent
active
058560955
ABSTRACT:
Mutants of thiopurine S-methyltransferase (TPMT) are described. TPMTA mutant has a point mutation at cDNA position 238 (G.sup.238 .fwdarw.C), and TPMTB involves two nucleotide transitions at cDNA positions 460 (G.sup.460 .fwdarw.A) and 719 (A.sup.719 .fwdarw.G). TPMTB is the predominant mutant allele associated with human TPMT-deficiency which can cause potentially fatal toxicity when patients are treated with mercaptopurine, azathioprine, or thioguanine. The mutant alleles as well as PCR fragments, mutant proteins and antibodies therefor, together with kits and methods for assaying the TPMT genotype of individual patients are disclosed.
REFERENCES:
patent: 5470737 (1995-11-01), Weinshilboum
The Bochringer Mahnheim Catalog (1989) p. 144.
Chomczynski, P., and Sacchi, N., "Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction," Analyt. Biochem. 162:156-159 (1987).
Ciechanover, A., and Schwartz, A.L., "The Ubiquitin-Mediated Proteolytic Pathway: Mechanisms of Recognition of the Proteolytic Substrate and Involvement in the Degradation of Native Cellular Proteins," FASEB J. 8:182-191 (Feb. 1994).
Evans, W.E., et al., "Altered Mercaptopurine Metabolism, Toxic Effects, and Dosage Requirement in a Thiopurine Methyltransferase-Deficient Child with Acute Lymphocytic Leukemia," J. Pediatr. 119(6):985-989 (1991).
Grant, D.M., "Molecular Genetics of the N-Acetyltransferases," Pharmacogenetics 3:45-50 (1993).
Heim, M., and Meyer, U.A., "Genotyping of Poor Metabolisers of Debrisoquine by Allele-Specific PCR Amplification," Lancet 336:529-532 (1990).
Hollander, A.A.M.J., et al., "Beneficial Effects of Conversion from Cyclosporin to Azathioprine After Kidney Transplantation," Lancet 345:610-614 (Mar. 11, 1995).
Honchel, R., et al., "Human Thiopurine Methyltransferase: Molecular Cloning and Expression of T84 Colon Carcinoma Cell cDNA," Molec. Pharmacol 43:878-887 (1993).
Jin. A., et al., "New Restriction Endonuclease CviRI Cleaves DNA at TG/CA Sequences," Nucl. Acids Res. 22(19):3928-3929 (Sep. 25, 1994).
Kohler, G., and Milstein, C., "Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity," Nature 256:495-497 (1975).
Krynetski, E.Y., et al., "A Single Point Mutation Leading to Loss of Catalytic Activity in Human Thiopurine S-methyltransferase," Proc. Natl. Acad. Sci. USA 92:949-953 (Feb. 1995).
Krynetski, E.Y., et al., "High Yield Expression of Functionally Active Human Liver CYP2D6 in Yeast Cells," Pharmacogenetics 5(2):103-109 (Apr. 1995).
Krynetski, E.Y., et al., "Methylation of Mercaptopurine, Thioguanine, and Their Nucleotide Metabolites by Heterologously Expressed Human Thiopurine S-Methyltransferase," Mol. Pharmacol. 47:1141-1147 (Jun. 1995).
Krynetsky, E.Yu., et al., "Effects of Amino-Terminus Truncation in Human Cytochrome P450IID6 on Ints Insertion Into the Endoplasmic Reticulum Membrane of Saccharomyces cerevisiae," FEBS Lett. 336(1):87-89 (1993).
Lee, D., et al., "Thiopurine Methyltransferase Pharmacogenetics. Cloning of Human Liver cDNA and a Processed Pseudogene on Human Chromosome 18q21.1," Drug Metab. Disp. 23(3):398-405 (Mar. 1995).
Lennard, L., et al., "Thiopurine Pharmacogenetics in Leukemia: Correlation of Erythrocyte Thiopurine Methyltransferase Activity and 6-Thioguanine Nucleotide Concentrations," Clin. Pharmacol. Ther. 41(1):18-25 (1987).
Lennard, L., et al., "Congenital Thiopurine Methyltransferase Deficiency and 6-Mercaptopurine Toxicity During Treatment for Acute Lymphoblastic Leukemia," Arch. Dis. Child. 69:577-579 (1993).
McLeod, H.L., et al., "Azathioprine-Induced Myelosuppression in Thiopurine Methyltransferase Deficient Heart Transplant Recipient," Lancet 341:1151 (1993).
McLeod, H.L., et al., "Higher Activity of Polymorphic Thiopurine S-Methyltransferase in Erythrocytes From Neonates Compared to Adults," Pharmacogenetics 5(5):281-286 (Jul. 1995).
Pacifici, G.M., et al., "S-Methyltransferases in Human Intestine: Differential Distribution of the Microsomal Thiol Methyltransferase and Cytosolic Thiopurine Methyltransferase Along the Human Bowel," Xenobiotica 23:671-679 (1993).
Purmal, A.A., et al., "5-Hydroxypyrimidine Deoxynucleoside Triphosphates are More Efficiently Incorporated into DNA by Exonuclease-Free Klenow Fragment than 8-Oxopurine Deoxynucleoside Triphosphates," Nucl. Acids. Res. 22(19):3930-3935 (Sep. 25, 1994).
Schmitt, M.E., et al., "A Rapid and Simple Method For Preparation of RNA From Saccharomyces cerevisiae," Nucl. Acids Res. 18(10):3091-3092 (1990).
Schutz, E., et al., "Azathioprine-Induced Myelosuppression in Thiopurine Methyltransferase Deficient Heart Transplant Recipient," Lancet 341:436 (1993).
Siebert, P.D., et al., "An Improved PCR Method for Walking in Uncloned Genomic DNA," Nucl. Acids Res. 23(6):1087-1088 (Mar. 1995).
Van Loon, J.A., and Weinshilboum, R.M., "Thiopurine Methyltransferaes Isozymes in Human Renal Tissue," Drug Metab. Dispos. 18(5):632-638 (1990).
Van Loon, J.A., et al., "Human Kidney Thiopurine Methyltransferase. Photoaffinity Labeling with S-Adenosyl-L-Methionine," Biochem. Pharmacol. 44(4):775-785 (1992).
Weinshilboum, R.M., et al., "Human Erythrocyte Thiopurine Methyltransferase: Radiochemical Microassay and Biochemical Properties," Clin. Chim. Acta 85:323-333 (1978).
Weinshilboum, R.M., and Sladek, S.L., "Mercaptopurine Pharmacogenetics: Monogenic Inheritance of Erythrocyte Thiopurine Methyltransferase Activity," Am. J. Human Genet. 32:651-662 (1980).
Woodson, L.C., et al., "Pharmacogenetics of Human Thiopurine Methyltransferase: Kidney-Erythrocyte Correlation and Immuntitration Studies," J. Pharmacol. Exp. Ther. 222(1):174-181 (1982).
Evans William E.
Krynetski Eugene Y.
Myers Carla J.
St. Jude Children's Research Hospital
LandOfFree
Identification of two novel mutant alleles of human thiopurine S does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Identification of two novel mutant alleles of human thiopurine S, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Identification of two novel mutant alleles of human thiopurine S will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-860965