Phenotypic profiling of DPYD variations relevant to 5-fluorouracil sensitivity using real-time cellular analysis and in vitro measurement of enzyme activity

Cancer Research

Volumn 73, Issue 6, 2013, Pages 1958-1968

  Offer, Steven M ^a   Wegner, Natalie J ^a   Fossum, Croix ^a   Wang, Kangsheng ^a   Diasio, Robert B ^a  

^a MAYO CLINIC CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROPYRIMIDINE DEHYDROGENASE; FLUOROURACIL;

ALLELE; ARTICLE; COLORECTAL CANCER; DPYD GENE; ENZYME ACTIVITY; GENE DELETION; GENE EXPRESSION; GENE FUNCTION; GENETIC ANALYSIS; GENETIC VARIABILITY; HUMAN; HUMAN CELL; IN VITRO STUDY; ONCOGENE; PHENOTYPE; PRIORITY JOURNAL; WILD TYPE;

ANTIMETABOLITES, ANTINEOPLASTIC; BLOTTING, WESTERN; CELL LINE; DIHYDROURACIL DEHYDROGENASE (NADP); FLUOROURACIL; GENE FREQUENCY; HUMANS;

EID: 84875421741     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-3858     Document Type: Article

References (44)

1. Rich TA, Shepard RC, Mosley ST. Four decades of continuing innovation with fluorouracil: current and future approaches to fluorouracil chemoradiation therapy. J Clin Oncol 2004;22:2214-32.
2. MacMillan WE, Wolberg WH, Welling PG. Pharmacokinetics of fluorouracil in humans. Cancer Res 1978;38:3479-82.
3. Heggie GD, Sommadossi JP, Cross DS, Huster WJ, Diasio RB. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res 1987;47:2203-6.
4. Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330-8.
5. Harris BE, Song R, Soong SJ, Diasio RB. Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion. Cancer Res 1990;50:197-201.
6. Fleming RA, Milano G, Thyss A, Etienne MC, Renee N, Schneider M, et al. Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients. Cancer Res 1992;52:2899-902.
7. Etienne MC, Lagrange JL, Dassonville O, Fleming R, Thyss A, Renee N, et al. Population study of dihydropyrimidine dehydrogenase in cancer patients. J Clin Oncol 1994;12:2248-53.
8. Diasio RB, Beavers TL, Carpenter JT. Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J Clin Invest 1988;81: 47-51.
9. Harris BE, Carpenter JT, Diasio RB. Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. Cancer 1991;68: 499-501.
10. Tuchman M, Ramnaraine ML, O'Dea RF. Effects of uridine and thymidine on the degradation of 5-fluorouracil, uracil, and thymine by rat liver dihydropyrimidine dehydrogenase. Cancer Res 1985;45:5553-6.
11. Wadman SK, Berger R, Duran M, de Bree PK, Stoker-de Vries SA, Beemer FA, et al. Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. J Inherit Metab Dis 1985;8(Suppl 2):113-4.
12. Braakhekke JP, Renier WO, Gabreels FJ, De Abreu RA, Bakkeren JA, Sengers RC. Dihydropyrimidine dehydrogenase deficiency. Neurological aspects. J Neurol Sci 1987;78:71-7.
13. Wilcken B, Hammond J, Berger R, Wise G, James C. Dihydropyrimidine dehydrogenase deficiency - a further case. J Inherit Metab Dis 1985;8(Suppl 2):115-6.
14. Boisdron-Celle M, Remaud G, Traore S, Poirier AL, Gamelin L, Morel A, et al. 5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer Lett 2007;249:271-82.
15. Meinsma R, Fernandez-Salguero P, Van Kuilenburg AB, Van Gennip AH, Gonzalez FJ. Human polymorphism in drug metabolism: mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea. DNA Cell Biol 1995;14:1-6.
16. van Kuilenburg AB, Hausler P, Schalhorn A, Tanck MW, Proost JH, Terborg C, et al. Evaluation of 5-fluorouracil pharmacokinetics in cancer patients with a c.1905+1G>A mutation in DPYD by means of a Bayesian limited sampling strategy. Clin Pharmacokinet 2012;51: 163-74.
17. The single nucleotide polymorphism database (dbSNP) of nucleotide sequence variation. [cited 2012 Aug 2010]. Available from: http://www.ncbi.nlm. nih.gov/projects/SNP/snp-ref.cgi?showRare=on&chooseRs=coding&go= Go&locusld=1806.
18. Kleibl Z, Fidlerova J, Kleiblova P, Kormunda S, Bilek M, Bouskova K, et al. Influence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fluoropyrimidinerelated toxicity in patients with high-grade toxicity and patients with excellent tolerance of fluoropyrimidine-based chemotherapy. Neoplasma 2009;56:303-16.
19. Irelan JT, Wu MJ, Morgan J, Ke N, Xi B, Wang X, et al. Rapid and quantitative assessment of cell quality, identity, and functionality for cell-based assays using real-time cellular analysis. J Biomol Screen 2011;16:313-22.
20. Johnson MR, Hageboutros A, Wang K, High L, Smith JB, Diasio RB. Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 1999;5:2006-11.
21. Morel A, Boisdron-Celle M, Fey L, Soulie P, Craipeau MC, Traore S, et al. Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 2006;5:2895-904.
22. Johnson MR, Wang K, Diasio RB. Profound dihydropyrimidine dehydrogenase deficiency resulting from a novel compound heterozygote genotype. Clin Cancer Res 2002;8:768-74.
23. van Kuilenburg AB, Dobritzsch D, Meinsma R, Haasjes J, Waterham HR, Nowaczyk MJ, et al. Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure. Biochem J 2002;364:157-63.
24. Loganayagam A, Arenas-Hernandez M, Fairbanks L, Ross P, Sanderson JD, Marinaki AM. The contribution of deleterious DPYD gene sequence variants to fluoropyrimidine toxicity in British cancer patients. Cancer Chemother Pharmacol 2010;65:403-6.
25. Amstutz U, Farese S, Aebi S, Largiader CR. Dihydropyrimidine dehydrogenase gene variation and severe 5-fluorouracil toxicity: a haplotype assessment. Pharmacogenomics 2009;10:931-44.
26. Schwab M, Zanger UM, Marx C, Schaeffeler E, Klein K, Dippon J, et al. Role of genetic and nongenetic factors for fluorouracil treatmentrelated severe toxicity: a prospective clinical trial by the German 5- FU Toxicity Study Group. J Clin Oncol 2008;26:2131-8.
27. Gross E, Busse B, Riemenschneider M, Neubauer S, Seck K, Klein HG, et al. Strong association of a common dihydropyrimidine dehydrogenase gene polymorphism with fluoropyrimidine-related toxicity in cancer patients. PLoS ONE 2008;3:e4003.
28. Zhang H, Li YM, Jin X. DPYD*5 gene mutation contributes to the reducedDPYDenzymeactivity and chemotherapeutic toxicity of 5-FU: results from genotyping study on 75 gastric carcinoma and colon carcinoma patients. Med Oncol 2007;24:251-8.
29. Zhang XP, Bai ZB, Chen BA, Feng JF, Yan F, Jiang Z, et al. Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Chin Med J (Engl) 2012;125:741-6.
30. Lazar A, Mau-Holzmann UA, Kolb H, Reichenmiller HE, Riess O, Schomig E. Multiple organ failure due to 5-fluorouracil chemotherapy in a patient with a rare dihydropyrimidine dehydrogenase gene variant. Onkologie 2004;27:559-62.
31. Collie-Duguid ES, Etienne MC, Milano G, McLeod HL. Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics 2000;10:217-23.
32. Seck K, Riemer S, Kates R, Ullrich T, Lutz V, Harbeck N, et al. Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in a cohort of Caucasian individuals. Clin Cancer Res 2005;11:5886-92.
33. Gross E, Ullrich T, Seck K, Mueller V, de Wit M, von Schilling C, et al. Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected in cancer patients with 5-fluorouracil-related side effects. Hum Mutat 2003;22:498.
34. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH. Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene. J Inherit Metab Dis 1997;20:335-8.
35. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH. Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet 1997;101:333-8.
36. Grem JL, McAtee N, Murphy RF, BalisFM, SteinbergSM, Hamilton JM, et al. A pilot study of interferon alfa-2a in combination with fluorouracil plus high-dose leucovorin in metastatic gastrointestinal carcinoma. J Clin Oncol 1991;9:1811-20.
37. Fety R, Rolland F, Barberi-Heyob M, Hardouin A, Campion L, Conroy T, et al. Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas. Clin Cancer Res 1998;4:2039-45.
38. Vreken P, van Kuilenburg AB, Meinsma R, van Gennip AH. Dihydropyrimidine dehydrogenase deficiency. Identification of two novel mutations and expression of missense mutations in E. coli. Adv Exp Med Biol 1998;431:341-6.
39. Vreken P, van Kuilenburg AB, Meinsma R, Beemer FA, Duran M, van Gennip AH. Dihydropyrimidine dehydrogenase deficiency: a novel mutation and expression of missense mutations in E. coli. J Inherit Metab Dis 1998;21:276-9.
40. Georgiou G, Valax P. Expression of correctly folded proteins in Escherichia coli. Curr Opin Biotechnol 1996;7:190-7.
41. Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y. Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil. EMBO J 2001;20:650-60.
42. Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, et al. CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res 2011;39:D225-9.
43. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010;7:248-9.
44. Wei X, McLeod HL, McMurrough J, Gonzalez FJ, Fernandez-Salguero P. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest 1996;98:610-5.