Cancer Letters
Volume 291, Issue 1 , Pages 31-38 , 1 May 2010

Deletion of the WWOX gene and frequent loss of its protein expression in human osteosarcoma

  • Jilong Yang

      Affiliations

    • Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Hospital and Institute, Tianjin 30060, China
    • Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
  • ,
  • David Cogdell

      Affiliations

    • Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
  • ,
  • Da Yang

      Affiliations

    • Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 30060, China
  • ,
  • Limei Hu

      Affiliations

    • Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
  • ,
  • Haixin Li

      Affiliations

    • Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 30060, China
  • ,
  • Hong Zheng

      Affiliations

    • Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 30060, China
  • ,
  • Xiaoling Du

      Affiliations

    • Department of Diagnostics, Tianjin Medical University, Tianjin 30060, China
  • ,
  • Yi Pang

      Affiliations

    • Department of Pathology, Tianjin Medical University Cancer Hospital and Institute, Tianjin 30060, China
  • ,
  • Jonathan Trent

      Affiliations

    • Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
  • ,
  • Kexin Chen

      Affiliations

    • Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 30060, China
  • ,
  • Wei Zhang

      Affiliations

    • Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
    • Corresponding Author InformationCorresponding author. Address: Department of Pathology, Unit 85, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA. Tel.: +1 713 745 1103; fax: +1 713 792 5549.

Received 23 September 2009 ,Accepted 28 September 2009.

References 

  1. Płuciennik E, Kusińska R, Potemski P, Kubiak R, Kordek R, Bednarek AK. WWOX – the FRA16D cancer gene: expression correlation with breast cancer progression and prognosis. Eur. J. Surg. Oncol. 2006;32:53–157
  2. Donati V, Fontanini G, Dell’Omodarme M, Prati MC, Nuti S, Lucchi M, et al. WWOX expression in different histologic types and subtypes of non-small cell lung cancer. Clin. Cancer Res. 2007;13:884–891
  3. Ramos D, Abba M, López-Guerrero JA, Rubio J, Solsona E, Almenar S, et al. Low levels of WWOX protein immuno expression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours. Histopathology. 2008;52:831–839
  4. Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, et al. Loss of WWOX expression in gastric carcinoma. Clin. Cancer Res. 2004;10:3053–3058
  5. Aarhus M, Bruland O, Bredholt G, Lybaek H, Husebye ES, Krossnes BK, et al. Microarray analysis reveals down-regulation of the tumour suppressor gene WWOX and up-regulation of the oncogene TYMS in intracranial sporadic meningiomas. J. Neurooncol. 2008;88:251–259
  6. Lewandowska U, Zelazowski M, Seta K, Byczewska M, Pluciennik E, Bednarek AK. WWOX, the tumour suppressor gene affected in multiple cancers. J. Physiol. Pharmacol. 2009;60:47–56
  7. Gourley C, Paige AJ, Taylor KJ, Ward C, Kuske B, Zhang J, et al. WWOX gene expression abolishes ovarian cancer tumorigenicity in vivo and decreases attachment to fibronectin via integrin alpha3. Cancer Res. 2009;69:4835–4842
  8. Bloomston M, Kneile J, Butterfield M, Dillhoff M, Muscarella P, Ellison EC, et al. Coordinate loss of fragile gene expression in pancreatobiliary cancers: correlations among markers and clinical features. Ann. Surg. Oncol. 2009;16:2331–2338
  9. Bednarek AK, Keck-Waggoner CL, Daniel RL, Laflin KJ, Bergsagel PL, Kiguchi K, et al. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res. 2001;61:8068–8073
  10. Fabbri M, Iliopoulos D, Trapasso F, Aqeilan RI, Cimmino A, Zanesi N, et al. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc. Natl. Acad. Sci. USA. 2005;102:15611–15616
  11. Yang JL, Zhang W. WWOX tumor suppressor gene. Histol. Histopathol. 2008;23:877–882
  12. Aqeilan RI, Hassan MQ, A de Bruin, Hagan JP, Volinia S, Palumbo T, et al. The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. J. Biol. Chem. 2008;283:21629–21639
  13. Aqeilan RI, Trapasso F, Hussain S, Costinean S, Marshall D, Pekarsky Y, et al. Targeted deletion of WWOX reveals a tumor suppressor function. Proc. Natl. Acad. Sci. USA. 2007;104:3949–3954
  14. Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer. 2009;115:1531–1543
  15. Selvarajah S, Yoshimoto M, Ludkovski O, Park PC, Bayani J, Thorner P, et al. Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH. Cytogenet. Genome Res. 2008;122:5–15
  16. Atiye J, Wolf M, Kaur S, Monni O, Böhling T, Kivioja A, et al. Gene amplifications in osteosarcoma-CGH microarray analysis. Genes Chromosomes Cancer. 2005;42:158–163
  17. Sadikovic B, Yoshimoto M, Al-Romaih K, Maire G, Zielenska M, Squire JA. In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma. PLoS One. 2008;3:e2834
  18. Maire G, Yoshimoto M, Chilton-MacNeill S, Thorner PS, Zielenska M, Squire JA. Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. Neoplasia. 2009;11:260–268
  19. Lu XY, Lu Y, Zhao YJ, Jaeweon K, Kang J, Xiao-Nan L, et al. Cell cycle regulator gene CDC5L, a potential target for 6p12–p21 amplicon in osteosarcoma. Mol. Cancer Res. 2008;6:937–946
  20. dos Santos Aguiar S, de Jesus Girotto Zambaldi L, dos Santos AM, Pinto W, Brandalise SR. Comparative genomic hybridization analysis of abnormalities in chromosome 21 in childhood osteosarcoma. Cancer Genet. Cytogenet. 2007;175:35–40
  21. Raymond AK, Ayala AG, Knuutila S. Conventional osteosarcoma. In:  Fletcher CDM,  Unni KK,  Mertens F editor. World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of Soft Tissue and Bone [M]. first ed.. Lyon, France: IARC Press; 2002;p. 264–270
  22. Sztán M, Pápai Z , Szendrôi M, Looij M, Oláh E. Allelic losses from chromosome 17 in human osteosarcomas. Pathol. Oncol. Res. 1997;3:115–120
  23. Feugeas O, Guriec N, Babin-Boilletot A, Marcellin L, Simon P, Babin S, et al. Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma. J. Clin. Oncol. 1996;14:467–472
  24. Heinsohn S, Evermann U, Zur Stadt U, Bielack S, Kabisch H. Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. Int. J. Oncol. 2007;30:1205–1214
  25. Ohata N, Ito S, Yoshida A, Kunisada T, Numoto K, Jitsumori Y, et al. Highly frequent allelic loss of chromosome 6q16–23 in osteosarcoma: involvement of cyclin C in osteosarcoma. Int. J. Mol. Med. 2006;18:1153–1158
  26. Savola S, Nardi F, Scotlandi K, Picci P, Knuutila S. Microdeletions in 9p21.3 induce false negative results in CDKN2A FISH analysis of Ewing sarcoma. Cytogenet. Genome Res. 2007;119:21–26
  27. Boussen H, Mezzi F, Gamoudi A, Daldoul O, Ben Hamida H, Mezlini A, et al. Primary chemotherapy with the Rosen T10 protocol before conservative surgery in limb primitive osteosarcomas: results about 56 cases. Bull. Cancer. 2000;87:183–188
  28. Pimenta FJ, Gomes DA, Perdigão PF, Barbosa AA, Romano-Silva MA, Gomez MV, et al. Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas. Int. J. Cancer. 2006;118:1154–1158
  29. Squire JA, Pei J, Marrano P, Beheshti B, Bayani J, Lim G, et al. High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer. 2003;38:215–225
  30. Finnis M, Dayan S, Hobson L, Chenevix-Trench G, Friend K, Ried K, et al. Common chromosomal fragile site FRA16D mutation in cancer cells. Hum. Mol. Genet. 2005;14:1341–1349
  31. Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, et al. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. Hum. Mol. Genet. 2000;9:1651–1663
  32. Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM. WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3–24.1, a region frequently affected in breast cancer. Cancer Res. 2000;60:2140–2145
  33. Kuroki T, Trapasso F, Shiraishi T, Alder H, Mimori K, Mori M, et al. Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma. Cancer Res. 2002;62:2258–2260
  34. Kuroki T, Yendamuri S, Trapasso F, Matsuyama A, Aqeilan RI, Alder H, et al. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Clin. Cancer Res. 2004;10:2459–2465
  35. Yendamuri S, Kuroki T, Trapasso F, Henry AC, Dumon KR, Huebner K, et al. WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer. Cancer Res. 2003;63:878–881
  36. Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, et al. WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc. Natl. Acad. Sci. USA. 2001;98:11417–11422
  37. Iliopoulos D, Guler G, Han SY, Johnston D, Druck T, McCorkell KA, et al. Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Oncogene. 2005;24:1625–1633
  38. Nakayama S, Semba S, Maeda N, Matsushita M, Kuroda Y, Yokozaki H. Hypermethylation-mediated reduction of WWOX expression in intraductal papillary mucinous neoplasms of the pancreas. Br. J. Cancer. 2009;100:1438–1443
  39. Ishii H, Vecchione A, Furukawa Y, Sutheesophon K, Han SY, Druck T, et al. Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies. Mol. Cancer Res. 2003;1:940–947
  40. Villagra A, Gutiérrez J, Paredes R, Sierra J, Puchi M, Imschenetzky M, et al. Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts. J. Cell. Biochem. 2002;85:112–122
  41. Ulaner GA, Vu TH, Li T, Hu JF, Yao XM, Yang Y, et al. Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site. Hum. Mol. Genet. 2003;12:535–549

PII: S0304-3835(09)00617-X

doi: 10.1016/j.canlet.2009.09.018

Cancer Letters
Volume 291, Issue 1 , Pages 31-38 , 1 May 2010