Ovarian Cancer: Linking Genomics to New Target Discovery and Molecular Markers — The Way Ahead

  • Bryan T. Hennessy
  • Mandi Murph
  • Meera Nanjundan
  • Mark Carey
  • Nelly Auersperg
  • Jonas Almeida
  • Kevin R. Coombes
  • Jinsong Liu
  • Yiling Lu
  • Joe W. Gray
  • Gordon B. Mills
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Epithelial ovarian cancer (EOC) is the 4th leading cause of cancer deaths among USA women and the most common cause of death from gynecologic cancers (1,2). It arises from ovarian surface epithelial (OSE) cells, and is currently classified by surgical and histological appearance (see Table 1), although the predictive value of this morphologic classification is limited (3).


Ovarian Cancer Epithelial Ovarian Cancer Lynch Syndrome Circulate Tumor Cell Copy Number Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jemal A, et al. (2003) Cancer statistics, 2003. CA Cancer J Clin 53:5–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Cannistra SA (2004) Cancer of the ovary. N Engl J Med 351:2519–2529.PubMedCrossRefGoogle Scholar
  3. 3.
    Hennessy BT, Mills GB, et al. (2006) Ovarian cancer: Homeobox genes, autocrine/paracrine growth, and kinase signaling. Int J Biochem Cell Biol 38:1450–1456.PubMedCrossRefGoogle Scholar
  4. 4.
    Taylor HS, Vanden Heuvel GB, Igarashi P (1997) A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod 57:1338–1345.PubMedCrossRefGoogle Scholar
  5. 5.
    International Collaborative Ovarian Neoplasm Group (2002) 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 360:505–515.CrossRefGoogle Scholar
  6. 6.
    Suzuki S, Moore III DH, Ginzinger DG, et al. (2000) An approach to analysis of large-scale correlations between genome changes and clinical endpoints in ovarian cancer. Cancer Res 60:5382–5385.PubMedGoogle Scholar
  7. 7.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Levine DA, Bogomolniy F, Yee CJ, et al. (2005) Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res 11:2875–2878.PubMedCrossRefGoogle Scholar
  9. 9.
    Campbell IG, Russell SE, Choong DY, et al. (2004) Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64:7678–7681.PubMedCrossRefGoogle Scholar
  10. 10.
    Shih IeM, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164:1511–1518.PubMedGoogle Scholar
  11. 11.
    Narod SA, Boyd J (2002) Current understanding of the epidemiology and clinical implications of BRCA1 and BRCA2 mutations for ovarian cancer. Curr Opin Obstet Gynecol 14:19–26.PubMedCrossRefGoogle Scholar
  12. 12.
    Stephens P, Edkins S, Davies H, et al. (2005) A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer. Nat Genet 37:590–592.PubMedCrossRefGoogle Scholar
  13. 13.
    Sjoblom T, Jones S, Wood LD, et al. (2006) The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science 314:268–274.PubMedCrossRefGoogle Scholar
  14. 14.
    Orsulic S, Li Y, Soslow RA, et al. (2002). Induction of ovarian cancer by defined multiple genetic changes in a mouse model system. Cancer Cell 1:53–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Dinulescu DM, Ince TA, Quade BJ, et al. (2005) Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 11:63–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Yang G, Rosen DG, Mercado-Uribe I, et al. (2007) Knockdown of p53 combined with expression of the catalytic subunit of telomerase is sufficient to immortalize primary human ovarian surface epithelial cells. Carcinogenesis 28:174–182.PubMedCrossRefGoogle Scholar
  17. 17.
    Alvero AB, Fishman DA, Qumsiyeh MB, et al. (2004) Telomerase prolongs the lifespan of normal human ovarian surface epithelial cells without inducing neoplastic phenotype. J Soc Gynecol Investig 11:553–561.PubMedCrossRefGoogle Scholar
  18. 18.
    Auersperg N, Wong AS, Choi KC, et al. (2001) Ovarian surface epithelium: biology, endocrinology and pathology. Endocr Rev 22:255–288.PubMedCrossRefGoogle Scholar
  19. 19.
    Zeimet AG, Marth C (2003) Why did p53 gene therapy fail in ovarian cancer? Lancet Oncol 4:415–422.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang TL, Maierhofer C, Speicher MR, et al. (2002) Digital karyotyping. Proc Natl Acad Sci USA 99:16156–16161.PubMedCrossRefGoogle Scholar
  21. 21.
    Shih IeM, Sheu JJ, Santillan A, et al. (2005) Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma. Proc Natl Acad Sci USA 102:14004–14009.PubMedCrossRefGoogle Scholar
  22. 22.
    Hennessy BT, Nanjunden M, Cheng KW, Nolden L, Mills GB (2006) Ovarian cancer: identification of remodeling and spacing factor 1 (rsf-1, HBXAP) at chromosome 11q13 as a putative oncogene in ovarian cancer (News and Commentary). Eur J Hum Genet 14:381–383.PubMedCrossRefGoogle Scholar
  23. 23.
    Watanabe T, Imoto I, Kosugi Y, et al. (2001) A novel amplification at 17q21–23 in ovarian cancer cell lines detected by comparative genomic hybridization. Gynecol Oncol 81:172–177.PubMedCrossRefGoogle Scholar
  24. 24.
    Shayesteh L, Lu Y, Kuo WL, et al. (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21:99–102.PubMedCrossRefGoogle Scholar
  25. 25.
    Cheng KW, Lahad JP, Kuo WL, et al. (2004) The Rab 25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 10:1251–1256.PubMedCrossRefGoogle Scholar
  26. 26.
    Eder A, Sui X, Rosen D, et al. (2005) Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA 102:12519–12524.PubMedCrossRefGoogle Scholar
  27. 27.
    Brown LA, Irving J, Parker R, et al. (2006) Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas. Gynecol Oncol 100:264–70.PubMedCrossRefGoogle Scholar
  28. 28.
    Hughes-Davies L, Huntsman D, Ruas M, et al. (2003) EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer. Cell 115:523–535.PubMedCrossRefGoogle Scholar
  29. 29.
    Anand N, Murthy S, Amann G, et al. (2002) Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nat Genet 31:301–305.PubMedGoogle Scholar
  30. 30.
    Schraml P, Schwerdtfeger G, Burkhalter F, et al. (2003) Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5–q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol 163:985–992.PubMedGoogle Scholar
  31. 31.
    Li P, Maines-Bandiera S, Kuo WL, et al. (2007) Multiple roles of the candidate oncogene znf217 in ovarian epithelial neoplastic progression. Int J Cancer 120:1863–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Kamikihara T, Arima T, Kato K, et al. (2005) Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer. Int J Cancer 115:690–700.PubMedCrossRefGoogle Scholar
  33. 33.
    Strathdee G, Appleton K, Illand M, et al. (2001) Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes. Am J Pathol 158:1121–1127.PubMedGoogle Scholar
  34. 34.
    Wei SH, Balch C, Paik HH, et al. (2006) Prognostic DNA methylation biomarkers in ovarian cancer. Clin Cancer Res 12:2788–2794.PubMedCrossRefGoogle Scholar
  35. 35.
    Wright JD, Hagemann A, Rader JS, et al. (2006) Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: a retrospective analysis. Cancer 107:83–89.PubMedCrossRefGoogle Scholar
  36. 36.
    Smith DI (2002) Transcriptional profiling develops molecular signatures for ovarian tumors. Cytometry 47:60–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Nanjundan M, Zhang F, Schmandt R, Smith-McCune K, Mills GB (2007) Identification of a novel splice variant of AML1b in ovarian cancer patients conferring loss of wild-type tumor suppressive functions. Oncogene 26:2574–84.PubMedCrossRefGoogle Scholar
  38. 38.
    Charboneau L, Scott H, Chen T, et al. (2002) Utility of reverse phase protein arrays: applications to signalling pathways and human body arrays. Brief Funct Genomic Proteomic 1:305–315.PubMedCrossRefGoogle Scholar
  39. 39.
    Sheehan KM, Calvert VS, Kay EW, et al. (2005) Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma. Mol Cell Proteomics 4:346–355.PubMedCrossRefGoogle Scholar
  40. 40.
    Tibes R, Qiu Y, Lu Y, et al. (2006) Reverse phase protein array (RPPA): validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoetic stem cells (HSC). Mol Cancer Ther 5:2512–21.PubMedCrossRefGoogle Scholar
  41. 41.
    Duffy MJ (2006) Serum tumor markers in breast cancer: are they of clinical value? Clin Chem 52:345–351.PubMedCrossRefGoogle Scholar
  42. 42.
    Kozak KR, Su F, Whitelegge JP, et al. (2005) Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics 5:4589–4596.PubMedCrossRefGoogle Scholar
  43. 43.
    Judson PL, Geller MA, Bliss RL, et al. (2003) Preoperative detection of peripherally circulating cancer cells and its prognostic significance in ovarian cancer. Gynecol Oncol 91:389–394.PubMedCrossRefGoogle Scholar
  44. 44.
    Swisher EM, Wollan M, Mahtani SM, et al. (2005) Specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. Am J Obstet Gynecol 193:662–667.PubMedCrossRefGoogle Scholar
  45. 45.
    Cristofanilli M, Budd GT, Ellis MJ, et al. (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. New Engl J Med 351:781–791.PubMedCrossRefGoogle Scholar
  46. 46.
    Muller V, Stahmann N, Riethdorf S, et al. (2005) Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Can Res 11:3678–3685.CrossRefGoogle Scholar
  47. 47.
    Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4:988–1004.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang X, Gorlitsky R, Almeida JS (2005) From XML to RDF: how semantic web technologies will change the design of ‘omic’ standards. Nat Biotechnol 23:1099–1103.PubMedCrossRefGoogle Scholar
  49. 49.
    Almeida JS, C Chen, R Gorlitsky, et al. (2006) Data integration gets ‘Sloppy’. Nat Biotechnol 24:1070–1071.PubMedCrossRefGoogle Scholar
  50. 50.
    Cheng W, Liu J, Yoshida H, et al. (2005) Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 11:531–537.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Bryan T. Hennessy
  • Mandi Murph
  • Meera Nanjundan
  • Mark Carey
  • Nelly Auersperg
  • Jonas Almeida
  • Kevin R. Coombes
  • Jinsong Liu
  • Yiling Lu
  • Joe W. Gray
  • Gordon B. Mills
    • 1
  1. 1.Department of Molecular TherapeuticsMD Anderson Cancer CenterHoustonUSA

Personalised recommendations