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Polymorphisms in the p53 pathway

Oncogene volume 25, pages 1602–1611 (2006)Cite this article

Abstract

The p53 tumor suppressor gene continues to be distinguished as the most frequently mutated gene in human cancer; this gene can be found mutated in up to 50% of human tumors of diverse histological type. It is generally accepted that the ability of p53 to induce either growth arrest or programmed cell death in response to diverse stimuli underlies the powerful selection against this protein in the development of cancer. It is somewhat surprising, then, to find p53 and several target genes in this pathway containing polymorphisms that impair their function. The nature of these polymorphic variants, and the mechanism whereby they impair the function of the p53 pathway, are reviewed here-in. The impact of these polymorphisms on cancer risk and the efficacy of therapy are only now becoming unraveled. Of particular relevance in these efforts will be the generation of mouse models of polymorphic variants in p53 and its target genes. Equally important will be better-controlled human studies, where-in haplotypes for p53 (that is, combinations of different polymorphisms in the p53 gene) and for p53-target genes are taken into account, instead of analyses of single gene variants, which have largely predominated to date. Studies in both regards should shed light on an emerging area in cancer biology, the significance of inter-individual differences in genotype on cancer risk, prognosis, and the efficacy of cancer therapy.

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References

  • Arva NC, Gopen TR, Talbott KE, Campbell LE, Chicas A, White DE et al. (2005). J Biol Chem 280: 26776–26787.

  • Bahl R, Arora S, Nath N, Mathur M, Shukla NK, Ralhan R . (2000). Oncogene 19: 323–328.

  • Bastiaens MT, Struyk L, Tjong-A-Hung SP, Gruis N, ter Huurne J, Westendorp RG et al. (2001). Mol Carcinog 30: 56–61.

  • Beckman G, Birgander R, Sjalander A, Saha N, Holmberg PA, Kivela A et al. (1994). Hum Hered 44: 266–270.

  • Bhatia K, Fan S, Spangler G, Weintraub M, O’Connor PM, Judde JG et al. (1995). Cancer Res 55: 1431–1435.

  • Birgander R, Sjalander A, Saha N, Spitsyn V, Beckman L, Beckman G . (1996). Hum Hered 46: 148–154.

  • Biro E, Kalina I, Salagovic J, Habalova V, Hriv ak M, Valansky L . (2000). Neoplasma 47: 303–306.

  • Biros E, Kalina I, Kohut A, Stubna J, Salagovic J . (2001). Lung Cancer 31: 157–162.

  • Biros E, Kohut A, Biros I, Kalina I, Bogyiova E, Stubna J . (2002). Lung Cancer 35: 231–235.

  • Bonafe M, Ceccarelli C, Farabegoli F, Santini D, Taffurelli M, Barbi C et al. (2003). Clin Cancer Res 9: 4860–4864.

  • Bonafe M, Salvioli S, Barbi C, Mishto M, Trapassi C, Gemelli C et al. (2002). Biochem Biophys Res Commun 299: 539–541.

  • Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC et al. (2004). Cell 119: 591–602.

  • Bougeard G, Baert-Desurmont S, Tournier I, Vasseur S, Martin C, Brugieres L et al. (2005). J Med Genet October 28; [Epub: ahead of print].

  • Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ . (1995). Nature 377: 552–557.

  • Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E et al. (1999). EMBO J 18: 6845–6854.

  • Buyru N, Tezol A, Dalay N . (2005). Anticancer Res 25: 2767–2769.

  • Buyru N, Tigli H, Dalay N . (2003). Oncol Rep 10: 711–714.

  • Chedid M, Michieli P, Lengel C, Huppi K, Givol D . (1994). Oncogene 9: 3021–3024.

  • Chen J, Jackson PK, Kirschner MW, Dutta A . (1995). Nature 374: 386–388.

  • Chen WC, Wu HC, Hsu CD, Chen HY, Tsai FJ . (2002). Urol Oncol 7: 63–66.

  • Chen YC, Xu L, Guo YL, Su HJ, Hsueh YM, Smith TJ et al. (2003). J Environ Sci Health A Tox Hazard Subst Environ Eng 38: 201–211.

  • Cobrinik D . (2005). Oncogene 24: 2796–2809.

  • de Oliveira WR, Rady PL, Grady J, Hughes TK, Neto CF, Rivitti EA et al. (2004). Int J Dermatol 43: 489–493.

  • Deng C, Zhang P, Harper JW, Elledge SJ, Leder P . (1995). Cell 82: 675–684.

  • Deshpande A, Sicinski P, Hinds PW . (2005). Oncogene 24: 2909–2915.

  • Dokianakis DN, Koumantaki E, Billiri K, Spandidos DA . (2000). Int J Mol Med 5: 405–409.

  • Dumont P, Leu JI, Della Pietra III AC, George DL, Murphy M . (2003). Nat Genet 33: 357–365.

  • el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM et al. (1993). Cell 19: 817–825.

  • Facher EA, Becich MJ, Deka A, Law JC . (1995). Cancer 79: 2424–2429.

  • Fan R, Wu MT, Miller D, Wain JC, Kelsey KT, Wiencke JK et al. (2000). Cancer Epidemiol Biomarkers Prev 9: 1037–1042.

  • Felley-Bosco E, Weston A, Cawley HM, Bennett WP, Harris CC . (1993). Am J Hum Genet 3: 752–759.

  • Fiszer-Maliszewska L, Kazanowska B, Kusnierczyk P, Manczak M, Niepieklo W, Pochron-Zeman B et al. (2003). J Appl Genet 44: 547–552.

  • Flores-Rozas H, Kelman Z, Dean FB, Pan ZQ, Harper JW, Elledge SJ et al. (1994). Proc Natl Acad Sci USA 91: 8655.

  • Gao X, Chen YQ, Wu N, Grignon DJ, Sakr W, Porter AT et al. (1995). Oncogene 11: 1395–1398.

  • Gemignani F, Moreno V, Landi S, Moullan N, Chabrier A, Gutierrez-Enriquez S et al. (2004). Oncogene 23: 1954–1956.

  • Gong JZ, Zhou H, Hu Z, Schulman P, Vinceguerra V, Broome JD et al. (1995). Hematol Pathol 9: 171–177.

  • Gottschlich S, Maune S, Preugschat J, Hoffmann M, Werner JA, Maass JD et al. (2000). Anticancer Res 20: 2613–2616.

  • Granja F, Morari J, Morari EC, Correa LA, Assumpcao LV, Ward LS . (2004). Cancer Lett 210: 151–157.

  • Gu Y, Turck CW, Morgan DO . (1993). Nature 366: 707–710.

  • Hachiya T, Kuriaki Y, Ueoka Y, Nishida J, Kato K, Wake N . (1999). Gynecol Oncol 72: 187–192.

  • Harima Y, Sawada S, Nagata K, Sougawa M, Ostapenko V, Ohnishi T . (2001). Int J Mol Med 7: 261–264.

  • Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ . (1993). Cell 75: 805–816.

  • Harris N, Brill E, Shohat O, Prokocimer M, Wolf D, Arai N et al. (1986). Mol Cell Biol 6: 4650–4656.

  • Harris CC, Hollstein MC . (1993). N Engl J Med 329: 1318–1327.

  • Henner WD, Evans AJ, Hough KM, Harris EL, Lowe BA, Beer TM . (2001). Prostate 49: 263–266.

  • Hillebrandt S, Streffer C, Demidchik EP, Biko J, Reiners C . (1997). Mutat Res 381: 201–207.

  • Huang SP, Wu WJ, Chang WS, Wu MT, Chen YY, Chen YJ et al. (2004). Cancer Epidemiol Biomarkers Prev 13: 2217–2224.

  • Huppi K, Siwarski D, Dosik J, Michieli P, Chedid M, Reed S et al. (1994). Oncogene 9: 3017–3020.

  • Jin S, Levine AJ . (2001). J Cell Sci 114: 4139–4140.

  • Jones JS, Chi X, Gu X, Lynch PM, Amos CI, Frazier ML . (2004). Clin Cancer Res 10: 5845–5849.

  • Kang S, Duan LH, Zhang JH, Guo W, Wang N, Li Y . (2004). Zhonghua Fu Chan Ke Za Zhi 39: 754–758 (Chinese).

  • Kawaguchi H, Ohno S, Araki K, Miyazaki M, Saeki H, Watanabe M et al. (2000). Cancer Res 60: 2753–2755.

  • Keshava C, Frye BL, Wolff MS, McCanlies EC, Weston A . (2002). Cancer Epidemiol Biomarkers Prev 11: 127–130.

  • Khaliq S, Hameed A, Khaliq T, Ayub Q, Qamar R, Mohyuddin A et al. (2000). Genet Test 4: 23–29.

  • Khrunin AV, Tarskaia LA, Spitsyn VA, Lylova OI, Bebyakova NA, Mikulich AI et al. (2005). Mol Genet Genomics 272: 666–672.

  • Kibel AS, Suarez BK, Belani J, Oh J, Webster R, Brophy-Ebbers M et al. (2003). Cancer Res 63: 2033–2036.

  • Klug SJ, Wilmotte R, Santos C, Almonte M, Herrero R, Guerrero I et al. (2001). Cancer Epidemiol Biomarkers Prev 10: 1009–1012.

  • Konishi R, Sakatani S, Kiyokane K, Suzuki K . (2000). J Dermatol Sci 24: 177–183.

  • Koopmann J, Maintz D, Schild S, Schramm J, Louis DN, Wiestler OD et al. (1995). Br J Cancer 72: 1230–1233.

  • Koushik A, Platt RW, Franco EL . (2004). Cancer Epidemiol Biomarkers Prev 13: 11–22. Review.

  • Kuroda Y, Tsukino H, Nakao H, Imai H, Katoh T . (2003). Cancer Lett 189: 77–83.

  • Langerod A, Bukholm IR, Bregard A, Lonning PE, Andersen TI, Rognum TO et al. (2002). Cancer Epidemiol Biomarkers Prev 11: 1684–1688.

  • Law JC, Deka A . (1995). Hum Genet 95: 459–460.

  • Lehman TA, Haffty BG, Carbone CJ, Bishop LR, Gumbs AA, Krishnan S et al. (2000). Cancer Res 60: 1062–1069.

  • Leu JI, Dumont P, Hafey M, Murphy ME, Georges DL . (2004). Nat Cell Biol 6: 443–450.

  • Li R, Waga S, Hannon GJ, Beach D, Stillman B . (1994). Nature 371: 534–537.

  • Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME . (2005). J Biol Chem 280: 24245–24251.

  • Li YJ, Laurent-Puig P, Salmon RJ, Thomas G, Hamelin R . (1995). Oncogene 10: 599–601.

  • Lukas J, Groshen S, Saffari B, Niu N, Reles A, Wen WH et al. (1997). Am J Pathol 150: 167–175.

  • Luo JL, Yang Q, Tong WM, Hergenhahn M, Wang ZQ, Hollstein M . (2001). Oncogene 20: 320–328.

  • Maga G, Hubscher U . (2003). J Cell Sci 116: 3051–3060.

  • Makni H, Franco EL, Kaiano J, Villa LL, Labrecque S, Dudley R et al. (2000). Int J Cancer 87: 528–533.

  • Marchenko ND, Zaika A, Moll UM . (2000). J Biol Chem 275: 16202–16212.

  • Marin MC, Jost CA, Brooks LA, Irwin MS, O’Nions J, Tidy JA et al. (2000). Nat Genet 25: 47–54.

  • Massague J . (2004). Nature 432: 298–306.

  • Matlashewski GJ, Tuck S, Pim D, Lamb P, Schneider J, Crawford LV . (1987). Mol Cell Biol 7: 961–963.

  • McKenzie KE, Siva A, Maier S, Runnebaum IB, Seshadri R, Sukumar S . (1997). Clin Cancer Res 3: 1669–1673.

  • Milner BJ, Hosking L, Sun S, Haites NE, Foulkes WD . (1996). Eur J Cancer 32A: 2360–2363.

  • Mitra S, Misra C, Singh RK, Panda CK, Roychoudhury S . (2005). J Clin Pathol 58: 26–31.

  • Mousses S, Ozcelik H, Lee PD, Malkin D, Bull SB, Andrulis IL . (1995). Hum Mol Genet 4: 1089–1092.

  • Nelson HH, Wilkojmen M, Marsit CJ, Kelsey KT . (2005). Carcinogenesis 26: 1770–1773.

  • Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T et al. (2000). Cell 102: 849–862.

  • Ohayon T, Gershoni-Baruch R, Papa MZ, Distelman Menachem T, Eisenberg Barzilai S, Friedman E . (2005). Br J Cancer 92: 1144–1148.

  • Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y et al. (2001). Mol Cell 8: 85–94.

  • Olivier M, Eclcs R, Hollstein M, Khan MA, Harris CC, Hainaut P . (2002). Hum Mutat 19: 607–614.

  • Pegoraro RJ, Rom L, Lanning PA, Moodley M, Naiker S, Moodley J . (2002). Int J Gynecol Cancer 12: 383–388.

  • Phelps M, Darley M, Primrose JN, Blaydes JP . (2003). Cancer Res 63: 2616–2623.

  • Pim D, Banks L . (2004). Int J Cancer 108: 196–199.

  • Powell BL, van Staveren IL, Roosken P, Grieu F, Berns EM, Iacopetta B . (2002). Carcinogenesis 23: 311–315.

  • Ralhan R, Agarwal S, Mathur M, Wasylyk B, Srivastava A . (2000). Clin Cancer Res 6: 2440–2447.

  • Rodrigues FC, Kawasaki-Oyama RS, Fo JF, Ukuyama EE, Antonio JR, Bozola AR et al. Cancer Genet Cytogenet 142: 92–98.

  • Roh JW, Kim JW, Park NH, Song YS, Park IA, Park SY et al. (2004). Gynecol Oncol 93: 499–505.

  • Roh JW, Kim MH, Kim JW, Park NH, Song YS, Kang SB et al. (2001). Cancer Lett 165: 59–62.

  • Runnebaum IB, Tong XW, Konig R, Zhao H, Korner K, Atkinson EN et al. (1995). Lancet 345: 994. Erratum in: Lancet 345, 1250.

  • Sakamuro D, Sabbatini P, White E, Prendergast GC . (1997). Oncogene 15: 887–898.

  • Sanchez-Prieto R, Rojas JM, Taya Y, Gutkind JS . (2000). Cancer Res 60: 2464–2472.

  • Schuler M, Green DR . (2005). Trends Genet 21: 182–187.

  • Shen H, Liu Z, Strom SS, Spitz MR, Lee JE, Gershenwald JE et al. (2003). J Invest Dermatol 121: 1510–1514.

  • Shen H, Solari A, Wang X, Zhang Z, Xu Y, Wang L et al. (2004). Oncol Rep 11: 1115–1120.

  • Shen H, Zheng Y, Sturgis EM, Spitz MR, Wei Q . (2002). Cancer Lett 183: 123–130.

  • Shi Y, Zou M, Farid NR, al-Sedairy ST . (1996). Br J Cancer 74: 1336–1341.

  • Shih CM, Lin PT, Wang HC, Huang WC, Wang YC . (2000). Jpn J Cancer Res 91: 9–15.

  • Shiohara M, el-Deiry WS, Wada M, Nakamaki T, Takeuchi S, Yang R et al. (1994). Blood 84: 3781–3784.

  • Sjalander A, Birgander R, Kivela A, Beckman G . (1995). Hum Hered 45: 144–149.

  • Sjalander A, Birgander R, Rannug A, Alexandrie AK, Tornling G, Beckman G . (1996). Hum Hered 46: 221–225.

  • Soulitzis N, Sourvinos G, Dokianakis DN, Spandidos DA . (2002). Cancer Lett 179: 175–183.

  • Sourvinos G, Rizos E, Spandidos DA . (2001). Oral Oncol 37: 572–578.

  • Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F et al. (1998). Nature 393: 229–234.

  • Su L, Liu G, Zhou W, Xu LL, Miller DP, Park S et al. (2003a). Cancer Epidemiol Biomarkers Prev 12: 174–175.

  • Su L, Sai Y, Fan R, Thurston SW, Miller DP, Zhou W et al. (2003b). Lung Cancer 40: 259–266.

  • Sullivan A, Syed N, Gasco M, Bergamaschi D, Trigiante G, Attard M et al. (2004). Oncogene 23: 3328–3337.

  • Sun Y, Hildesheim A, Li H, Li Y, Chen JY, Cheng YJ et al. (1995). Cancer Epidemiol Biomarkers Prev 4: 261–267.

  • Suzuki K, Matsui H, Ohtake N, Nakata S, Takei T, Nakazato H et al. (2003). J Biomed Sci 10: 430–435.

  • Takekawa M, Adachi M, Nakahata A, Nakayama I, Itoh F, Tsukuda H et al. (2000). EMBO J 19: 6517–6526.

  • Terry LA, Boyd J, Alcorta D, Lyon T, Solomon G, Hannon G et al. (1996). Mol Carcinog 16: 221–228.

  • Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G . (1999). Mol Cell Biol 19: 1092–1100.

  • Tiwawech D, Srivatanakul P, Karaluk A, Ishida T . (2003). Cancer Lett 198: 69–75.

  • Tommiska J, Eerola H, Heinonen M, Salonen L, Kaare M, Tallila J et al. (2005). Clin Cancer Res 11: 5098–5103.

  • Tsai MH, Chen WC, Tsai FJ . (2002a). J Clin Lab Anal 16: 146–150.

  • Tsai MH, Lin CD, Hsieh YY, Chang FC, Tsai FJ, Chen WC et al. (2002b). Laryngoscope 112: 116–119.

  • Vikhanskaya F, Siddique MM, Kei Lee M, Broggini M, Sabapathy K . (2005). Clin Cancer Res 11: 4348–4356.

  • Waga S, Hannon GJ, Beach D, Stillman B . (1994). Nature 369: 574–578.

  • Walker KK, Levine AJ . (1996). Proc Natl Acad Sci USA 93: 15335–15340.

  • Wan M, Cofer KF, Dubeau L . (1996). Br J Cancer 73: 1398–1400.

  • Wang YC, Chen CY, Chen SK, Chang YY, Lin P . (1999). Clin Cancer Res 5: 129–134.

  • Wang-Gohrke S, Weikel W, Risch H, Vesprini D, Abrahamson J, Lerman C et al. (1999). Br J Cancer 81: 179–183.

  • Weston A, Godbold JH . (1997). Environ Health Perspect 4: 919–926.

  • Wu MT, Chen MC, Wu DC . (2004). Cancer Lett 205: 61–68.

  • Wu MT, Wu DC, Hsu HK, Kao EL, Yang CH, Lee JM . (2003). Cancer Lett 201: 175–180.

  • Wu X, Zhao H, Amos CI, Shete S, Makan N, Hong WK et al. (2002). J Natl Cancer Inst 94: 681–690.

  • Xi YG, Ding KY, Su XL, Chen DF, You WC, Shen Y et al. (2004). Carcinogenesis 25: 2201–2206.

  • Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D . (1993). Nature 366: 701–704.

  • Xu Y, Yao L, Ouyang T, Li J, Wang T, Fan Z et al. (2005). Clin Cancer Res 11: 7328–7333.

  • Zhang JH, Li Y, Wang R, Wen DG, Wu ML, He M . (2003). Zhonghua Zhong Liu Za Zhi 25: 365–367. (Chinese).

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  1. E C Pietsch and O Humbey: These authors contributed equally to this work.

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  1. Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, PA, USA

    E C Pietsch, O Humbey & M E Murphy

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Pietsch, E., Humbey, O. & Murphy, M. Polymorphisms in the p53 pathway. Oncogene 25, 1602–1611 (2006). https://doi.org/10.1038/sj.onc.1209367

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