Journal of Cancer Research and Clinical Oncology

, Volume 132, Issue 1, pp 19–27

Identification of a candidate tumor suppressor gene RHOBTB1 located at a novel allelic loss region 10q21 in head and neck cancer

  • Levent B. Beder
  • Mehmet Gunduz
  • Mamoru Ouchida
  • Esra Gunduz
  • Akiko Sakai
  • Kunihiro Fukushima
  • Hitoshi Nagatsuka
  • Sachio Ito
  • Noriyasu Honjo
  • Kazunori Nishizaki
  • Kenji Shimizu
Original Paper

Abstract

Purpose: Aims of the study are to narrow-down the hotspot region on 10q21 defined by previous genome-wide loss of heterozygosity (LOH) analysis in head and neck squamous cell carcinomas (HNSCC) and to define candidate tumor suppressor genes (TSG) concerned with 10q21. Materials and methods: LOH analysis was carried out with ten polymorphic microsatellite markers. Expression analysis was performed by semi-quantitative RT-PCR, and mutation analysis by PCR and direct sequencing. Results: LOH analysis on 10q21 in 52 HNSCC indicated distinctive and frequent allelic loss at D10S589 (42%). Among flanking genes, we found the RHOBTB1 gene as a candidate TSG, since an intragenic marker demonstrated the highest LOH (44%). Expression analysis revealed down-regulation of RHOBTB1 mRNA in 37% of tumors. Interestingly, all the five tumors that showed decreased expression of RHOBTB1 were accompanied with LOH, supporting the haploinsufficiency and class 2 TSG characteristics of RHOBTB1. No pathogenic mutation of RHOBTB1 was found. Furthermore, another gene within the region, EGR2, was also taken under scope. LOH frequencies around the EGR2 gene were relatively low (23 and 33%). Albeit semi-quantitative expression analysis of EGR2 demonstrated downregulation in 45% of tumor samples, no relation was found between the expression levels and LOH status. Conclusion: Frequent allelic loss and decreased expression of RHOBTB1 suggested that this gene has a role in tumorigenesis of a subset of HNSCC.

Keywords

10q21 RHOBTB1 EGR2 LOH analysis RT-PCR 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Levent B. Beder
    • 1
  • Mehmet Gunduz
    • 2
  • Mamoru Ouchida
    • 3
  • Esra Gunduz
    • 2
  • Akiko Sakai
    • 3
  • Kunihiro Fukushima
    • 1
  • Hitoshi Nagatsuka
    • 2
  • Sachio Ito
    • 3
  • Noriyasu Honjo
    • 1
  • Kazunori Nishizaki
    • 1
  • Kenji Shimizu
    • 3
  1. 1.Department of Otolaryngology, Graduate School of Medicine and DentistryOkayama UniversityOkayamaJapan
  2. 2.Department of Oral Pathology and Medicine, Graduate School of Medicine and DentistryOkayama UniversityOkayamaJapan
  3. 3.Department of Molecular Genetics, Graduate School of Medicine and DentistryOkayama UniversityOkayamaJapan

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