Authors: Katase, Naoki; Gunduz, Mehmet; Beder, Levent; Gunduz, Esra; Lefeuvre, Mathieu; Hatipoglu, Omer Faruk; Borkosky, Silvia Susana; Tamamura, Ryo; Tominaga, Susumu; Yamanaka, Noboru; Shimizu, Kenji; Nagai, Noriyuki; Nagatsuka, Hitoshi

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Volume 17, Number 6, 2008 , pp. 273-282(10)

Publisher: Cognizant Communication Corporation

Abstract:

Head and neck squamous cell carcinoma (HNSCC) is a frequently occurring cancer, and despite improvement of its treatment methods, including chemotherapy, radiotherapy, and surgery, the improvement of survival remains poor. Recent advances in molecular biology of human cancer indicated various molecular abnormalities in HNSCC, including activation of oncogenes and inactivation of tumor suppressor genes (TSGs). Dickkopf (Dkk)-3 gene is known as a negative regulator of Wnt signaling and is suggested to function as TSG in several kinds of malignancies. We hypothesized that Dkk-3 might play an important role in HNSCC, too. Thus, in the current study, we analyzed allelic alteration of Dkk-3 locus (chromosome 11p15.2) by means of loss of heterozygosity (LOH) analysis. The study population consisted of 50 patients with HNSCC (mean age of 65 years old). Furthermore, we also examined the correlation between LOH findings of Dkk-3 locus with clinicopathological parameters to investigate its use as a biomarker in HNSCC. A remarkable LOH ratio (57%) was detected in the cases studied, implying that Dkk-3 is likely to be involved in HNSCC carcinogenesis. However, interestingly and in contrast to the expectations, we found that the group with LOH of Dkk-3 locus had less lymph node metastasis, and showed a favorable overall survival compared to the patients with retention of Dkk-3 area in survival analysis. These results indicate that Dkk-3 can play a role in HNSCC carcinogenesis with unknown mechanism. Moreover, allelic loss at Dkk-3 locus may also be used as a novel prognostic biomarker in HNSCC.

Keywords: Loss of heterozygosity; PCR; Dkk-3; Tumor suppressor gene; Head and neck squamous cell carcinoma; 11p15.2

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096504008786991594

Publication date: 2008-06-01

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• Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
  Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

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• By this author: Katase, Naoki ;  Gunduz, Mehmet ;  Beder, Levent ;  Gunduz, Esra ;  Lefeuvre, Mathieu ;  Hatipoglu, Omer Faruk ;  Borkosky, Silvia Susana ;  Tamamura, Ryo ;  Tominaga, Susumu ;  Yamanaka, Noboru ;  Shimizu, Kenji ;  Nagai, Noriyuki ;  Nagatsuka, Hitoshi

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