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WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi

Year 2020, Volume: 8 Issue: 2, 258 - 263, 23.08.2020
https://doi.org/10.37696/nkmj.682726

Abstract

Amaç: WW alanı içeren oksidoredüktaz (WWOX) geni kromozom 16q23.3-q24.1 bölgesinde bulunmaktadır ve yaygın kromozomal frajil bölge, FRA16D, içermektedir. WWOX geni 46 kDa moleküler ağırlığında Wwox tümör baskılayıcı proteini kodlar. Birçok insan kanserlerinde WWOX lokusunda heterozigozite kaybı (LOH), WWOX promoter hipermetilasyonu ve sonuç olarak Wwox ifadesi kaybı veya azalması bildirilmiştir. Ayrıca, son çalışmalar çeşitli kanser tiplerinde Wwox eksikliğinin kötü prognoz ile ilişkili olduğunu göstermiştir. Kronik lenfositik löseminin (KLL) klinik özelliklleri ve genetik anomalileri iyi tanımlanmıştır, fakat moleküler detaylar halen araştırılmaktadır. WWOX ifadesi seviyeleri KLL için olası bir biyobelirteç olabilir. Bildiğimiz kadarıyla literatürde KLL’de WWOX’ın tanı ve prognostik önemi ile ilgili kanıtlar bulunmamaktadır. Çalışmamızda, KLL hastalarında ve sağlıklı kontrollerde WWOX ifadesi düzeylerini tanımlamayı ve KLL hastalarında WWOX ifadesini klinik özelliklerine göre analiz etmeyi amaçladık. Materyal ve Metot: Bu çalışma 40 KLL hastasında ve 26 sağlıklı kontrolde gerçekleştirildi. WWOX ifadesi seviyeleri ters transkriptaz-kantitatif PCR (RT-QPCR) tekniği kullanarak analiz edildi. Bulgular: WWOX ifadesinin KLL hastalarında sağlıklı kontrol grubuna göre anlamlı derecede yüksek olduğunu bulduk (P<0,001). WWOX düzeyleri ile KLL'deki klinik parametreler arasında istatistiksel olarak anlamlı bir fark saptadık (P>0,05). Sonuçlar: Sonuç olarak, WWOX geninin anormal transkripsiyon varyantları, anormal protein izoformları ile ilişkilendirilebilir ve bu izoformlar, KLL hastalarında WWOX geninin tümör baskılayıcı etkilerini değiştirebilir.

Supporting Institution

Bu çalışma Tekirdağ Namık Kemal Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir.

Project Number

NKUBAP.02.YL.17.137

Thanks

Bu çalışma Tekirdağ Namık Kemal Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir (NKUBAP.02.YL.17.137).

References

  • 1. Aldaz CM, Ferguson BW, Abba MC. WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies. Biochim Biophys Acta 2014;1:188-200.
  • 2. Bednarek AJ, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM. WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3–16q24.1, a region frequently affected in breast cancer. Cancer Res 2000;60:2140-5.
  • 3. Aqeilan RI, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarskym Y ve ark. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res 2005;15:6764-72.
  • 4. Schrock MS, Batar B, Lee J, Druck T, Ferguson B, Cho JH ve ark. Wwox-BRCA1 interaction: role in DNA repair pathway choice. Oncogene 2017;36:2215-27.
  • 5. Abu-Odeh M, Salah Z, Herbel C, Hofmann TG, Aqeilan RI. WWOX, the common fragile site FRA16D gene product, regulatesATM activation and the DNA damage response. Proc NatlAcad Sci USA 2014;111:E4716-E4725.
  • 6. Aqeilan RI, Hagan JP, de Bruin A, Rawahneh M, Salah Z, Gaudio E ve ark. Targeted ablation of the WW domaincontaining oxidoreductase tumor suppressor leads to impaired steroidogenesis. Endocrinology 2009;3:1530-5.
  • 7. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J ve ark. The landscape of somatic copynumber alteration across human cancers. Nature 2010;18:899–905.
  • 8. Wang X, Chao L, Jin G, Ma G, Zang Y, Sun J. Association between CpG island methylation of the WWOX gene and its expression in breast cancers. Tumour Biol 2009;30:8-14. 9. Guo W, Wang G, Dong Y, Guo Y, Kuang G, Dong Z. Decreased expression of WWOX in the development of esophageal squamous cell carcinoma. Mol Carcinog 2013;52:265-74.
  • 10. 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;100:1438-43.
  • 11. Dias EP, Pimenta FJ, Sarquis MS, Dias Filho MA, Aldaz CM, Fujii JB, Gomez RS, De Marco L.. Association between decreased WWOX protein expression and thyroid cancer development. Thyroid 2007;17:1055-9.
  • 12. Yang J, Cogdell D, Yang D, Hu L, Li H, Zheng H, Du X, Pang Y, Trent J, Chen K, Zhang W. Deletion of the WWOX gene and frequent loss of its protein expression in human osteosarcoma. Cancer Lett 2010;291:31-8.
  • 13. Ishii H, Vecchione A, Furukawa Y, Sutheesophon K, Han SY, Druck T, Kuroki T, Trapasso F, Nishimura M, Saito Y, Ozawa K, Croce CM, Huebner K, Furukawa. Expression of FRA16D/ WWOX and FRA3B/FHIT genes in hematopoietic malignancies. Mol Cancer Res 2003;1:940-7.
  • 14. Ishii H, Furukawa Y: Alterations of common chromosome fragile sites in hematopoietic malignancies. Int J Hematol 2044;79:238-42.
  • 15. Nunez, M. I., Rosen, D. G., Ludes-Meyers, J. H., Abba, M. C., Kil, H., Page, R., Klein-Szanto, A. J., Godwin, A. K., Liu, J., Mills, G. B. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer 2005;5(1):64.
  • 16. Guler, G., Huebner, K., Himmetoglu, C., Jimenez, R. E., Costinean, S., Volinia, S., Pilarski, R. T., Hayran, M., Shapiro, C. L. Fragile histidine triad protein, WW domain containing oxidoreductase protein Wwox, and activator protein 2γ expression levels correlate with basal phenotype in breast cancer. Cancer: Interdisciplinary International Journal of the American Cancer Society, 2009;115:899-908.
  • 17. Rodríguez D, Bretones G, Arango JR, Valdespino V, Campo E, Quesada V, López-Otín C. Molecular pathogenesis of CLL and its evolution. Int J Hematol. 2015;101:219-28.
  • 18. Aqeilan RI, Abu-Remaileh M, Abu-Odeh M. The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability. Cell Mol Life Sci, 2014;71(23):4589-99.
  • 19. Schrock MS, Huebner K. WWOX: A fragile tumor suppressor. Exp Biol Med (Maywood), 2015;240:296-304.
  • 20. Lo JY, Chou YT, Lai FJ, Hsu LJ. Regulation of cell signaling and apoptosis by tumor suppressor WWOX. Exp Biol Med (Maywood), 2015;240:383-91.
  • 21. Ludes-Meyers JH, Bednarek AK, Popescu NC, Bedford M, Aldaz CM. WWOX, the common chromosomal fragile site, FRA16D, cancer gene. Cytogenet Genome Res, 2003;100(1-4):101-10.
  • 22. Adam JW, Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE. WWOX: A candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci USA, 2001;98:11417-22.
Year 2020, Volume: 8 Issue: 2, 258 - 263, 23.08.2020
https://doi.org/10.37696/nkmj.682726

Abstract

Project Number

NKUBAP.02.YL.17.137

References

  • 1. Aldaz CM, Ferguson BW, Abba MC. WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies. Biochim Biophys Acta 2014;1:188-200.
  • 2. Bednarek AJ, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM. WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3–16q24.1, a region frequently affected in breast cancer. Cancer Res 2000;60:2140-5.
  • 3. Aqeilan RI, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarskym Y ve ark. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res 2005;15:6764-72.
  • 4. Schrock MS, Batar B, Lee J, Druck T, Ferguson B, Cho JH ve ark. Wwox-BRCA1 interaction: role in DNA repair pathway choice. Oncogene 2017;36:2215-27.
  • 5. Abu-Odeh M, Salah Z, Herbel C, Hofmann TG, Aqeilan RI. WWOX, the common fragile site FRA16D gene product, regulatesATM activation and the DNA damage response. Proc NatlAcad Sci USA 2014;111:E4716-E4725.
  • 6. Aqeilan RI, Hagan JP, de Bruin A, Rawahneh M, Salah Z, Gaudio E ve ark. Targeted ablation of the WW domaincontaining oxidoreductase tumor suppressor leads to impaired steroidogenesis. Endocrinology 2009;3:1530-5.
  • 7. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J ve ark. The landscape of somatic copynumber alteration across human cancers. Nature 2010;18:899–905.
  • 8. Wang X, Chao L, Jin G, Ma G, Zang Y, Sun J. Association between CpG island methylation of the WWOX gene and its expression in breast cancers. Tumour Biol 2009;30:8-14. 9. Guo W, Wang G, Dong Y, Guo Y, Kuang G, Dong Z. Decreased expression of WWOX in the development of esophageal squamous cell carcinoma. Mol Carcinog 2013;52:265-74.
  • 10. 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;100:1438-43.
  • 11. Dias EP, Pimenta FJ, Sarquis MS, Dias Filho MA, Aldaz CM, Fujii JB, Gomez RS, De Marco L.. Association between decreased WWOX protein expression and thyroid cancer development. Thyroid 2007;17:1055-9.
  • 12. Yang J, Cogdell D, Yang D, Hu L, Li H, Zheng H, Du X, Pang Y, Trent J, Chen K, Zhang W. Deletion of the WWOX gene and frequent loss of its protein expression in human osteosarcoma. Cancer Lett 2010;291:31-8.
  • 13. Ishii H, Vecchione A, Furukawa Y, Sutheesophon K, Han SY, Druck T, Kuroki T, Trapasso F, Nishimura M, Saito Y, Ozawa K, Croce CM, Huebner K, Furukawa. Expression of FRA16D/ WWOX and FRA3B/FHIT genes in hematopoietic malignancies. Mol Cancer Res 2003;1:940-7.
  • 14. Ishii H, Furukawa Y: Alterations of common chromosome fragile sites in hematopoietic malignancies. Int J Hematol 2044;79:238-42.
  • 15. Nunez, M. I., Rosen, D. G., Ludes-Meyers, J. H., Abba, M. C., Kil, H., Page, R., Klein-Szanto, A. J., Godwin, A. K., Liu, J., Mills, G. B. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer 2005;5(1):64.
  • 16. Guler, G., Huebner, K., Himmetoglu, C., Jimenez, R. E., Costinean, S., Volinia, S., Pilarski, R. T., Hayran, M., Shapiro, C. L. Fragile histidine triad protein, WW domain containing oxidoreductase protein Wwox, and activator protein 2γ expression levels correlate with basal phenotype in breast cancer. Cancer: Interdisciplinary International Journal of the American Cancer Society, 2009;115:899-908.
  • 17. Rodríguez D, Bretones G, Arango JR, Valdespino V, Campo E, Quesada V, López-Otín C. Molecular pathogenesis of CLL and its evolution. Int J Hematol. 2015;101:219-28.
  • 18. Aqeilan RI, Abu-Remaileh M, Abu-Odeh M. The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability. Cell Mol Life Sci, 2014;71(23):4589-99.
  • 19. Schrock MS, Huebner K. WWOX: A fragile tumor suppressor. Exp Biol Med (Maywood), 2015;240:296-304.
  • 20. Lo JY, Chou YT, Lai FJ, Hsu LJ. Regulation of cell signaling and apoptosis by tumor suppressor WWOX. Exp Biol Med (Maywood), 2015;240:383-91.
  • 21. Ludes-Meyers JH, Bednarek AK, Popescu NC, Bedford M, Aldaz CM. WWOX, the common chromosomal fragile site, FRA16D, cancer gene. Cytogenet Genome Res, 2003;100(1-4):101-10.
  • 22. Adam JW, Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE. WWOX: A candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci USA, 2001;98:11417-22.
There are 21 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Orginal Article
Authors

Halil Hancı This is me 0000-0002-0457-287X

Birol Topçu 0000-0003-0771-2505

Seval Akpınar This is me 0000-0002-6961-8971

Burhan Turgut 0000-0001-5729-0043

Bahadir Batar 0000-0001-8760-8411

Project Number NKUBAP.02.YL.17.137
Publication Date August 23, 2020
Published in Issue Year 2020 Volume: 8 Issue: 2

Cite

APA Hancı, H., Topçu, B., Akpınar, S., Turgut, B., et al. (2020). WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi. Namık Kemal Tıp Dergisi, 8(2), 258-263. https://doi.org/10.37696/nkmj.682726
AMA Hancı H, Topçu B, Akpınar S, Turgut B, Batar B. WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi. NKMJ. August 2020;8(2):258-263. doi:10.37696/nkmj.682726
Chicago Hancı, Halil, Birol Topçu, Seval Akpınar, Burhan Turgut, and Bahadir Batar. “WWOX Gen İfadesinin Kronik Lenfositik Lösemi Ile İlişkisi”. Namık Kemal Tıp Dergisi 8, no. 2 (August 2020): 258-63. https://doi.org/10.37696/nkmj.682726.
EndNote Hancı H, Topçu B, Akpınar S, Turgut B, Batar B (August 1, 2020) WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi. Namık Kemal Tıp Dergisi 8 2 258–263.
IEEE H. Hancı, B. Topçu, S. Akpınar, B. Turgut, and B. Batar, “WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi”, NKMJ, vol. 8, no. 2, pp. 258–263, 2020, doi: 10.37696/nkmj.682726.
ISNAD Hancı, Halil et al. “WWOX Gen İfadesinin Kronik Lenfositik Lösemi Ile İlişkisi”. Namık Kemal Tıp Dergisi 8/2 (August 2020), 258-263. https://doi.org/10.37696/nkmj.682726.
JAMA Hancı H, Topçu B, Akpınar S, Turgut B, Batar B. WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi. NKMJ. 2020;8:258–263.
MLA Hancı, Halil et al. “WWOX Gen İfadesinin Kronik Lenfositik Lösemi Ile İlişkisi”. Namık Kemal Tıp Dergisi, vol. 8, no. 2, 2020, pp. 258-63, doi:10.37696/nkmj.682726.
Vancouver Hancı H, Topçu B, Akpınar S, Turgut B, Batar B. WWOX Gen İfadesinin Kronik Lenfositik Lösemi ile İlişkisi. NKMJ. 2020;8(2):258-63.