Note: References 39–50 are cited in the Supporting information to this article.

  • 1
    Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nature Rev Cancer 2009; 9: 701713.
  • 2
    Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 1991; 51: 29792984.
  • 3
    Okamoto A, Sameshima Y, Yokoyama S, Terashima Y, Sugimura T, Terada M, et al. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res 1991; 51: 51715176.
  • 4
    de Graeff P, Crijns AP, de Jong S, Boezen M, Post WJ, de Vries EG, et al. Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis. Br J Cancer 2009; 101: 149159.
  • 5
    Hall J, Paul J, Brown R. Critical evaluation of p53 as a prognostic marker in ovarian cancer. Expert Rev Mol Med 2004; 6: 120.
  • 6
    Soussi T, Ishioka C, Claustres M, Beroud C. Locus-specific mutation databases: pitfalls and good practice based on the p53 experience. Nature Rev Cancer 2006; 6: 8390.
  • 7
    Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, et al. A candidate precursor to serous carcinoma that originates in the distal Fallopian tube. J Pathol 2007; 211: 2635.
  • 8
    Crum CP, Drapkin R, Miron A, Ince TA, Muto M, Kindelberger DW, et al. The distal Fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 2007; 19: 39.
  • 9
    Jordan SJ, Green AC, Whiteman DC, Moore SP, Bain CJ, Gertig DM, et al. Serous ovarian, Fallopian tube and primary peritoneal cancers: a comparative epidemiological analysis. Int J Cancer 2008; 122: 15981603.
  • 10
    Herrington CS, McCluggage WG. The emerging role of the distal Fallopian tube and p53 in pelvic serous carcinogenesis. J Pathol 2007; 220: 56.
  • 11
    McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 2005; 97: 11801184.
  • 12
    Olivier M, Petitjean A, Marcel V, Petre A, Mounawar M, Plymoth A, et al. Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Ther 2009; 16: 112.
  • 13
    Montes de Oca Luna R, Wagner DS, Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 1995; 378: 203206.
  • 14
    Parant J, Chavez-Reyes A, Little NA, Yan W, Reinke V, Jochemsen AG, et al. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nature Genet 2001; 29: 9295.
  • 15
    Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 1992; 358: 8083.
  • 16
    McCann AH, Kirley A, Carney DN, Corbally N, Magee HM, Keating G, et al. Amplification of the MDM2 gene in human breast cancer and its association with MDM2 and p53 protein status. Br J Cancer 1995; 71: 981985.
  • 17
    Shahin MS, Hughes JH, Sood AK, Buller RE. The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma. Cancer 2000; 89: 20062017.
  • 18
    Olivier M, Langerod A, Carrieri P, Bergh J, Klaar S, Eyfjord J, et al. The clinical value of somatic TP53 gene mutations in 1794 patients with breast cancer. Clin Cancer Res 2006; 12: 11571167.
  • 19
    Muscolini M, Montagni E, Caristi S, Nomura T, Kamada R, Di Agostino S, et al. Characterization of a new cancer-associated mutant of p53 with a missense mutation (K351N) in the tetramerization domain. Cell Cycle 2009; 8: 33963405.
  • 20
    Vang R, Shih Ie M, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol 2009; 16: 267282.
  • 21
    Shih Ie M, Kurman RJ. Molecular pathogenesis of ovarian borderline tumors: new insights and old challenges. Clin Cancer Res 2005; 11: 72737279.
  • 22
    Meinhold-Heerlein I, Bauerschlag D, Hilpert F, Dimitrov P, Sapinoso LM, Orlowska-Volk M, et al. Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential. Oncogene 2005; 24: 10531065.
  • 23
    Salani R, Kurman RJ, Giuntoli R 2nd, Gardner G, Bristow R, Wang TL, et al. Assessment of TP53 mutation using purified tissue samples of ovarian serous carcinomas reveals a higher mutation rate than previously reported and does not correlate with drug resistance. Int J Gynecol Cancer 2008; 18: 487491.
  • 24
    Dehari R, Kurman RJ, Logani S, Shih IeM. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis. Am J Surg Pathol 2007; 31: 10071012.
  • 25
    Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003; 112: 779791.
  • 26
    Dornan D, Wertz I, Shimizu H, Arnott D, Frantz GD, Dowd P, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 2004; 429: 8692.
  • 27
    Bartel F, Jung J, Bohnke A, Gradhand E, Zeng K, Thomssen C, et al. Both germ line and somatic genetics of the p53 pathway affect ovarian cancer incidence and survival. Clin Cancer Res 2008; 14: 8996.
  • 28
    Darcy KM, Brady WE, McBroom JW, Bell JG, Young RC, McGuire WP, et al. Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers. A Gynecologic Oncology Group study. Gynecol Oncol 2008; 111: 487495.
  • 29
    Hogdall EV, Christensen L, Hogdall CK, Frederiksen K, Gayther S, Blaakaer J, et al. Distribution of p53 expression in tissue from 774 Danish ovarian tumour patients and its prognostic significance in ovarian carcinomas. APMIS 2008; 116: 400409.
  • 30
    Kupryjanczyk J, Kraszewska E, Ziolkowska-Seta I, Madry R, Timorek A, Markowska J, et al. TP53 status and taxane–platinum versus platinum-based therapy in ovarian cancer patients: a non-randomized retrospective study. BMC Cancer 2008; 8: 27.
  • 31
    Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356: 215221.
  • 32
    Terzian T, Suh YA, Iwakuma T, Post SM, Neumann M, Lang GA, et al. The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss. Genes Dev 2008; 22: 13371344.
  • 33
    Li Y, Guessous F, Kwon S, Kumar M, Ibidapo O, Fuller L, et al. PTEN has tumor-promoting properties in the setting of gain-of-function p53 mutations. Cancer Res 2008; 68: 17231731.
  • 34
    Phillips KA, Nichol K, Ozcelik H, Knight J, Done SJ, Goodwin PJ, et al. Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of BRCA1 mutations. J Natl Cancer Inst 1999; 91: 469473.
  • 35
    Holstege H, Joosse SA, van Oostrom CT, Nederlof PM, de Vries A, Jonkers J. High incidence of protein-truncating TP53 mutations in BRCA1-related breast cancer. Cancer Res 2009; 69: 36253633.
  • 36
    Turner N, Tutt A, Ashworth A. Hallmarks of ‘BRCAness’ in sporadic cancers. Nature Rev Cancer 2004; 4: 814819.
  • 37
    Zorn KK, Bonome T, Gangi L, Chandramouli GV, Awtrey CS, Gardner GJ, et al. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res 2005; 11: 64226430.
  • 38
    Kobel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 2008; 5: e232.
  • 39
    ICON. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 2002; 360: 505515.
  • 40
    Etemadmoghadam D, de Fazio A, Beroukhim R, Mermel C, George J, Getz G, et al. Integrated genome-wide DNA copy number and expression analysis identifies distinct mechanisms of primary chemoresistance in ovarian carcinomas. Clin Cancer Res 2009; 15: 14171427.
  • 41
    Rustin GJ, Nelstrop AE, McClean P, Brady MF, McGuire WP, Hoskins WJ, et al. Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125. J Clin Oncol 1996; 14: 15451551.
  • 42
    Vergote I, Rustin GJ, Eisenhauer EA, Kristensen GB, Pujade-Lauraine E, Parmar MK, et al. Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup. J Natl Cancer Inst 2000; 92: 15341535.
  • 43
    Kupryjanczyk J, Thor AD, Beauchamp R, Merritt V, Edgerton SM, Bell DA, et al. p53 gene mutations and protein accumulation in human ovarian cancer. Proc Natl Acad Sci U S A 1993; 90: 49614965.
  • 44
    Shimizu Y, Kamoi S, Amada S, Akiyama F, Silverberg SG. Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up. Cancer 1998; 82: 893901.
  • 45
    Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321: 18071812.
  • 46
    Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 2009; 174: 15971601.
  • 47
    Bengtsson H, Irizarry R, Carvalho B, Speed TP. Estimation and assessment of raw copy numbers at the single locus level. Bioinformatics 2008; 24: 759767.
  • 48
    Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000; 132: 365386.
  • 49
    Riemenschneider MJ, Buschges R, Wolter M, Reifenberger J, Bostrom J, Kraus JA, et al. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res 1999; 59: 60916096.
  • 50
    Wang TL, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW, et al. Digital karyotyping. Proc Natl Acad Sci U S A 2002; 99: 1615616161.