Production of truncated MBD4 protein by frameshift mutation in DNA mismatch repair-deficient cells enhances 5-fluorouracil sensitivity that is independent of hMLH1 status

Cancer Biology and Therapy

Volumn 17, Issue 7, 2016, Pages 760-768

  Suzuki, Satoshi ^a   Iwaizumi, Moriya ^a,b   Tseng Rogenski, Stephanie ^b   Hamaya, Yasushi ^a,b   Miyajima, Hiroaki ^a   Kanaoka, Shigeru ^c   Sugimoto, Ken ^a   Carethers, John M ^b  

^a HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c HAMAMATSU MEDICAL CENTER   (Japan)

Author keywords

5 fluorouracil; Colorectal cancer; cytotoxicity; DNA mismatch repair; frameshift mutation; MBD4; truncated protein

Indexed keywords

FLUOROURACIL; METHYL CPG BINDING PROTEIN; PROTEIN MLH1; TRUNCATED METHYL CPG BINDING DOMAIN PROTEIN 4 PROTEIN; UNCLASSIFIED DRUG; DEOXYRIBONUCLEASE; MBD4 PROTEIN, HUMAN; MLH1 PROTEIN, HUMAN; MUTL PROTEIN HOMOLOG 1;

ARTICLE; CANCER PATIENT; CANCER RESISTANCE; CELL CYCLE S PHASE; CELL GROWTH; COLORECTAL CANCER; CONTROLLED STUDY; CYTOTOXICITY; DRUG PROTEIN BINDING; DRUG SENSITIVITY; EXCISION REPAIR; FLOW CYTOMETRY; FRAMESHIFT MUTATION; GENE OVEREXPRESSION; HCT116 CELL LINE; HT 29 CELL LINE; HUMAN; HUMAN CELL; MISMATCH REPAIR; COLORECTAL NEOPLASMS; GENETIC TRANSFECTION; GENETICS; METABOLISM;

COLORECTAL NEOPLASMS; DNA MISMATCH REPAIR; ENDODEOXYRIBONUCLEASES; FLUOROURACIL; FRAMESHIFT MUTATION; HUMANS; MUTL PROTEIN HOMOLOG 1; TRANSFECTION;

EID: 84969753170     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.1080/15384047.2016.1178430     Document Type: Article

References (52)

1. C.G.Moertel, T.R.Fleming, J.S.Macdonald, D.G.Haller, J.A.Laurie, C.M.Tangen, J.S.Ungerleider, W.A.Emerson, D.C.Tormey, J.H.Glick, et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 1995; 122(5):321-6; PMID:7847642; http://dx.doi.org/10.7326/0003-4819-122-5-199503010-00001
2. C.G.Moertel, T.R.Fleming, J.S.Macdonald, D.G.Haller, J.A.Laurie, P.J.Goodman, J.S.Ungerleider, W.A.Emerson, D.C.Tormey, J.H.Glick, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990; 322(6):352-8; PMID:2300087; http://dx.doi.org/10.1056/NEJM199002083220602
3. C.R.Boland, F.A.Sinicrope, D.E.Brenner, J.M.Carethers. Colorectal cancer prevention and treatment. Gastroenterology 2000; 118(2 Suppl 1):S115-28; PMID:10868902; http://dx.doi.org/10.1016/S0016-5085(00)70010-2
4. J.M.Carethers. Systemic treatment of advanced colorectal cancer – tailoring therapy to the tumor. Ther Adv Gastroenterol 2008; 1:33-42; PMID:21180512; http://dx.doi.org/10.1177/1756283X08093607
5. Meta-analysis Group In Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol. 1998; 16(1):301-8; PMID:9440757
6. J.M.Carethers, E.J.Smith, C.A.Behling, L.Nguyen, A.Tajima, R.T.Doctolero, B.L.Cabrera, A.Goel, C.A.Arnold, K.Miyai, et al. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 2004; 126(2):394-401; PMID:14762775; http://dx.doi.org/10.1053/j.gastro.2003.12.023
7. R.Jover, P.Zapater, A.Castells, X.Llor, M.Andreu, J.Cubiella, F.Balaguer, L.Sempere, R.M.Xicola, L.Bujanda, et al. The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status. Eur J Cancer 2009; 45(3):365-73; PMID:18722765; http://dx.doi.org/10.1016/j.ejca.2008.07.016
8. C.M.Ribic, D.J.Sargent, M.J.Moore, S.N.Thibodeau, A.J.French, R.M.Goldberg, S.R.Hamilton, P.Laurent-Puig, R.Gryfe, L.E.Shepherd, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003; 349(3):247-57; PMID:12867608; http://dx.doi.org/10.1056/NEJMoa022289
9. Y.Hamaya, C.Guarinos, S.S.Tseng-Rogenski, M.Iwaizumi, R.Das, R.Jover, A.Castells, X.Llor, M.Andreu, J.M.Carethers. Efficacy of 5-fluorouracil adjuvant therapy for patients with EMAST-positive stage II/III colorectal cancers. PLoS One 2015; 10:e0127591; PMID:25996601; http://dx.doi.org/10.1371/journal.pone.0127591
10. G.T.Marsischky, R.D.Kolodner. Biochemical characterization of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 complex and mispaired bases in DNA. J Biol Chem 1999; 274(38):26668-82; PMID:10480869; http://dx.doi.org/10.1074/jbc.274.38.26668
11. J.M.Carethers, M.Koi, S.Tseng-Rogenski. EMAST is a form of microsatellite instability that is initiated by inflammation and modulates colorectal cancer progression. Genes 2015; 6:185-205; PMID:25836926; http://dx.doi.org/10.3390/genes6020185
12. S.Acharya, T.Wilson, S.Gradia, M.F.Kane, S.Guerrette, G.T.Marsischky, R.Kolodner, R.Fishel. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci USA 1996; 93(24):13629-34; PMID:8942985; http://dx.doi.org/10.1073/pnas.93.24.13629
13. L.J.Blackwell, K.P.Bjornson, P.Modrich. DNA-dependent activation of the hMutSalpha ATPase. J Biol Chem 1998; 273(48):32049-54; PMID:9822679; http://dx.doi.org/10.1074/jbc.273.48.32049
14. N.de Wind, M.Dekker, N.Claij, L.Jansen, Y.van Klink, M.Radman, G.Riggins, M.van der Valk, K.van't Wout, H.te Riele. HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. Nat Genet 1999; 23(3):359-62; PMID:10545954; http://dx.doi.org/10.1038/15544
15. J.Genschel, S.J.Littman, J.T.Drummond, P.Modrich. Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha. J Biol Chem 1998; 273(31):19895-901; PMID:9677427; http://dx.doi.org/10.1074/jbc.273.31.19895
16. Y.Habraken, P.Sung, L.Prakash, S.Prakash. Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3. Curr Biol 1996; 6(9):1185-7; PMID:8805366; http://dx.doi.org/10.1016/S0960-9822(02)70686-6
17. A.Umar, J.I.Risinger, W.E.Glaab, K.R.Tindall, J.C.Barrett, T.A.Kunkel. Functional overlap in mismatch repair by human MSH3 and MSH6. Genetics 1998; 148(4):1637-46; PMID:9560383
18. D.R.Duckett, J.T.Drummond, A.I.Murchie, J.T.Reardon, A.Sancar, D.M.Lilley, P.Modrich. Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct. Proc Natl Acad Sci USA 1996; 93(13):6443-7; PMID:8692834; http://dx.doi.org/10.1073/pnas.93.13.6443
19. A.Tajima, M.T.Hess, B.L.Cabrera, R.D.Kolodner, J.M.Carethers. The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA: implications for chemosensitivity and resistance. Gastroenterology 2004; 127(6):1678-84; PMID:15578504; http://dx.doi.org/10.1053/j.gastro.2004.10.001
20. A.Tajima, M.Iwaizumi, S.Tseng-Rogenski, B.L.Cabrera, J.M.Carethers. Both hMutSalpha and hMutSbeta DNA mismatch repair complexes participate in 5-Fluorouracil cytotoxicity. PLoS One 2011; 6(12):e28117; PMID:22164234; http://dx.doi.org/10.1371/journal.pone.0028117
21. F.Fischer, K.Baerenfaller, J.Jiricny. 5-Fluorouracil is efficiently removed from DNA by the base excision and mismatch repair systems. Gastroenterology 2007; 133(6):1858-68; PMID:18054558; http://dx.doi.org/10.1053/j.gastro.2007.09.003
22. H.Chung, J.Chaudhry, C.G.Lopez,, J.M.Carethers. Cyclin E and histone H3 are regulated by 5-fluorouracil in a DNA mismatch repair-dependent manner. Cancer Biol Ther 2010; 10:1147-56; PMID:20930505; http://dx.doi.org/10.4161/cbt.10.11.13447
23. M.Iwaizumi, S.Tseng-Rogenski, J.M.Carethers. DNA mismatch repair proficiency executing 5-fluorouracil cytotoxicity in colorectal cancer cells. Cancer Biol Ther 2011; 12(8):756-64; PMID:21814034; http://dx.doi.org/10.4161/cbt.12.8.17169
24. M.Iwaizumi, S.Tseng-Rogenski, J.M.Carethers. Acidic tumor microenvironment downregulates hMLH1 but does not diminish 5-fluorouracil chemosensitivity. Mutat Res 2013; 747-8:19-27; PMID:23643670; http://dx.doi.org/10.1016/j.mrfmmm.2013.04.006
25. S.Andersen, T.Heine, R.Sneve, I.Konig, H.E.Krokan, B.Epe, H.Nilsen. Incorporation of dUMP into DNA is a major source of spontaneous DNA damage, while excision of uracil is not required for cytotoxicity of fluoropyrimidines in mouse embryonic fibroblasts. Carcinogenesis 2005; 26(3):547-55; PMID:15564287; http://dx.doi.org/10.1093/carcin/bgh347
26. Q.An, P.Robins, T.Lindahl, D.E.Barnes. 5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity. Cancer Res 2007; 67(3):940-5; PMID:17283124; http://dx.doi.org/10.1158/0008-5472.CAN-06-2960
27. C.Kunz, F.Focke, Y.Saito, D.Schuermann, T.Lettieri, J.Selfridge, P.Schär. Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil. PLoS Biol 2009; 7(4):e91; PMID:19402749; http://dx.doi.org/10.1371/journal.pbio.1000091
28. O.J.Sansom, J.Zabkiewicz, S.M.Bishop, J.Guy, A.Bird, A.R.Clarke. MBD4 deficiency reduces the apoptotic response to DNA-damaging agents in the murine small intestine. Oncogene 2003; 22(46):7130-6; PMID:14562041; http://dx.doi.org/10.1038/sj.onc.1206850
29. B.Hendrich, U.Hardeland, H.H.Ng, J.Jiricny, A.Bird. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature 1999; 401(6750):301-4; PMID:10499592; http://dx.doi.org/10.1038/45843
30. F.Petronzelli, A.Riccio, G.D.Markham, S.H.Seeholzer, M.Genuardi, M.Karbowski, A.T.Yeung, Y.Matsumoto, A.Bellacosa. Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain. J Cell Physiol 2000; 185(3):473-80; PMID:11056019; http://dx.doi.org/10.1002/1097-4652(200012)185:3%3c473::AID-JCP19%3e3.0.CO;2-
31. F.Petronzelli, A.Riccio, G.D.Markham, S.H.Seeholzer, J.Stoerker, M.Genuardi, A.T.Yeung, Y.Matsumoto, A.Bellacosa. Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase. J Biol Chem 2000; 275(42):32422-9; PMID:10930409; http://dx.doi.org/10.1074/jbc.M004535200
32. S.Bader, M.Walker, B.Hendrich, A.Bird, C.Bird, M.Hooper, A.Wyllie. Somatic frameshift mutations in the MBD4 gene of sporadic colon cancers with mismatch repair deficiency. Oncogene 1999; 18(56):8044-7; PMID:10637515; http://dx.doi.org/10.1038/sj.onc.1203229
33. A.Riccio, L.A.Aaltonen, A.K.Godwin, A.Loukola, A.Percesepe, R.Salovaara, V.Masciullo, M.Genuardi, M.Paravatou-Petsotas, D.E.Bassi, et al. The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Nat Genet 1999; 23(3):266-8; PMID:10545939; http://dx.doi.org/10.1038/15443
34. T.Yamada, T.Koyama, S.Ohwada, K.Tago, I.Sakamoto, S.Yoshimura, K.Hamada, I.Takeyoshi, Y.Morishita. Frameshift mutations in the MBD4/MED1 gene in primary gastric cancer with high-frequency microsatellite instability. Cancer Lett 2002; 181(1):115-20; PMID:12430186; http://dx.doi.org/10.1016/S0304-3835(02)00043-5
35. S.A.Bader, M.Walker, D.J.Harrison. A human cancer-associated truncation of MBD4 causes dominant negative impairment of DNA repair in colon cancer cells. Br J Cancer 2007; 96(4):660-6; PMID:17285135; http://dx.doi.org/10.1038/sj.bjc.6603592
36. W.M.Abdel-Rahman, S.Knuutila, P.Peltomaki, D.J.Harrison, S.A.Bader. Truncation of MBD4 predisposes to reciprocal chromosomal translocations and alters the response to therapeutic agents in colon cancer cells. DNA Repair (Amst) 2008; 7(2):321-8; PMID:18162445; http://dx.doi.org/10.1016/j.dnarep.2007.11.009
37. M.Meyers, M.W.Wagner, A.Mazurek, C.Schmutte, R.Fishel, D.A.Boothman. DNA mismatch repair-dependent response to fluoropyrimidine-generated damage. J Biol Chem 2005; 280(7):5516-26; PMID:15611052; http://dx.doi.org/10.1074/jbc.M412105200
38. A.Bellacosa, L.Cicchillitti, F.Schepis, A.Riccio, A.T.Yeung, Y.Matsumoto, E.A.Golemis, M.Genuardi, G.Neri. MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Proc Natl Acad Sci USA 1999; 96(7):3969-74; PMID:10097147; http://dx.doi.org/10.1073/pnas.96.7.3969
39. J.M.Carethers, B.H.Jung. Genetics and genetic biomarkers in sporadic colorectal cancer. Gastroenterology 2015; 149:1177-90; PMID:26216840; http://dx.doi.org/10.1053/j.gastro.2015.06.047
40. H.Ashktorab, S.Ahuja, L.Kannan, X.Llor, N.Ellis, R.M.Xicola, L.O.Adeyinka, J.M.Carethers, H.Brim, M.Nouraie. A meta-analysis of MSI frequency and race in colorectal cancer. Oncotarget 2016; PMID:2710810; http://dx.doi.org/10.18632/oncotarget.8945
41. H.Chung, D.J.Young, C.Lopez, T.-A.T.Le, J.K.Lee, D.Ream-Robinson, S.C.Huang, J.M.Carethers. Mutation rates of TGFBR2 and ACVR2 coding microsatellites in human cells with defective DNA mismatch repair. PLoS One 2008; 3:e3463; PMID:18941508; http://dx.doi.org/10.1371/journal.pone.0003463
42. H.Chung, J.Chaudhry, J.F.Lai, D.J.Young, J.M.Carethers. Flanking nucleotide specificity for DNA mismatch repair-deficient frameshifts within Activin Receptor 2 (ACVR2). Mutat Res 2012; 729:73-80; PMID:22001236; http://dx.doi.org/10.1016/j.mrfmmm.2011.09.009
43. H.Chung, C.G.Lopez, J.Holmstrom, D.J.Young, J.F.Lai, D.Ream-Robinson, J.M.Carethers. Both microsatellite length and sequence context determine frameshift mutation rates in defective DNA mismatch repair. Hum Mol Genet 2010; 19:2638-4; PMID:20418486; http://dx.doi.org/10.1093/hmg/ddq151
44. H.Chung, C.G.Lopez, D.J.Young, J.F.Lai, J.Holmstrom, D.Ream-Robinson, B.L.Cabrera, J.M.Carethers. Flanking sequence specificity determines coding microsatellite heteroduplex and mutation rates with defective DNA mismatch repair. Oncogene 2010; 29:2172-80; PMID:20140012; http://dx.doi.org/10.1038/onc.2009.508
45. B.Jung, R.T.Doctolero, A.Tajima, A.K.Nguyen, T.Keku, R.S.Sandler, J.M.Carethers. Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers. Gastroenterology 2004; 126:654-59; PMID:14988818; http://dx.doi.org/10.1053/j.gastro.2004.01.008
46. F.Grigera, A.Bellacosa, A.L.Kenter. Complex relationship between mismatch repair proteins and MBD4 during immunoglobulin class switch recombination. PLoS One 2013; 8(10):e78370; PMID:24205214; http://dx.doi.org/10.1371/journal.pone.0078370
47. S.Cortellino, D.Turner, V.Masciullo, F.Schepis, D.Albino, R.Daniel, A.M.Skalka, N.J.Meropol, C.Alberti, L.Larue, et al. The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity. Proc Natl Acad Sci USA 2003; 100(25):15071-6; PMID:14614141; http://dx.doi.org/10.1073/pnas.2334585100
48. E.Wong, K.Yang, M.Kuraguchi, U.Werling, E.Avdievich, K.Fan, M.Fazzari, B.Jin, A.M.Brown, M.Lipkin, et al. Mbd4 inactivation increases Cright-arrowT transition mutations and promotes gastrointestinal tumor formation. Proc Natl Acad Sci USA 2002; 99(23):14937-42; PMID:12417741; http://dx.doi.org/10.1073/pnas.232579299
49. S.Bader, M.Walker, D.Harrison. Most microsatellite unstable sporadic colorectal carcinomas carry MBD4 mutations. Br J Cancer 2000; 83(12):1646-9; PMID:11104560; http://dx.doi.org/10.1054/bjoc.2000.1482
50. C.R.Boland, A.Goel. Microsatellite instability in colorectal cancer. Gastroenterology 2010; 138(6):2073-87.e3; PMID:20420947; http://dx.doi.org/10.1053/j.gastro.2009.12.064
51. J.M.Carethers, E.M.Stoffel. Lynch syndrome and Lynch syndrome mimics: the growing complex landscape of hereditary colon cancer. World J Gastroenterology 2015; 21:9253-61; PMID:26309352; http://dx.doi.org/10.3748/wjg.v21.i31.9253
52. A.Collura, A.Lagrange, M.Svrcek, L.Marisa, O.Buhard, A.Guilloux, K.Wanherdrick, C.Dorard, A.Taieb, A.Saget, et al. Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil-based chemotherapy. Gastroenterology 2014; 146(2):401-11.e1; PMID:24512910; http://dx.doi.org/10.1053/j.gastro.2013.10.054