BACKGROUND: Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC. METHODS: We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis. RESULTS: We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNbeta and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNalpha and/or D9S171 and D9S126 but not necessarily CDKN2. CONCLUSIONS: These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence.
BACKGROUND: Deletion of 9p21 is a common event in many humantumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC. METHODS: We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis. RESULTS: We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNbeta and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNalpha and/or D9S171 and D9S126 but not necessarily CDKN2. CONCLUSIONS: These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence.
Authors: Silvia S Borkosky; Mehmet Gunduz; Hitoshi Nagatsuka; Levent Bekir Beder; Esra Gunduz; Mahmoud A L Sheikh Ali; Andrea P Rodriguez; Mehmet Zeynel Cilek; Susumu Tominaga; Noboru Yamanaka; Kenji Shimizu; Noriyuki Nagai Journal: J Cancer Res Clin Oncol Date: 2008-11-08 Impact factor: 4.553
Authors: P Schraml; K Struckmann; R Bednar; W Fu; T Gasser; K Wilber; J Kononen; G Sauter; M J Mihatsch; H Moch Journal: Am J Pathol Date: 2001-02 Impact factor: 4.307
Authors: Maria J Worsham; Josena K Stephen; Kang Mei Chen; Shaleta Havard; Veena Shah; Glendon Gardner; Vanessa G Schweitzer Journal: Cancer Lett Date: 2012-03-01 Impact factor: 8.679
Authors: Josena K Stephen; Kang Mei Chen; Veena Shah; Vanessa G Schweitzer; Glendon Gardner; Michael S Benninger; Maria J Worsham Journal: Int J Head Neck Surg Date: 2010-05
Authors: Katerina I Leonova; Leonid Brodsky; Brittany Lipchick; Mahadeb Pal; Liliya Novototskaya; Alex A Chenchik; Ganes C Sen; Elena A Komarova; Andrei V Gudkov Journal: Proc Natl Acad Sci U S A Date: 2012-12-10 Impact factor: 11.205
Authors: Maria J Worsham; Josena K Stephen; Mei Lu; Kang Mei Chen; Shaleta Havard; Veena Shah; Vanessa P Schweitzer Journal: Otolaryngol Head Neck Surg Date: 2012-03-12 Impact factor: 3.497