PURPOSE: Amplification at chromosome 3q26.3 is a common and crucial event in head and neck squamous cell carcinoma (HNSCC), impacting significantly on tumor progression and clinical outcome. Two novel oncogenes, namely squamous cell carcinoma (SCC)-related oncogene (SCCRO) and PIK3CA (gene encoding phosphatidylinositol-3 kinase catalytic alpha-polypeptide), have been identified as targets of 3q26.3 amplification. This study aimed to delineate the role of SCCRO and PIK3CA in the pathogenesis of oral tongue SCC. EXPERIMENTAL DESIGN: The association between gene copy number for SCCRO and PIK3CA measured by fluorescence in situ hybridization and level of mRNA expression quantitated by real-time reverse transcription-PCR was assessed in a panel of human HNSCC cell lines. In addition, gene expression in 49 consecutive primary SCCs of the oral tongue was determined and correlated with clinicopathological characteristics and outcome. RESULTS: The mRNA level of SCCRO and PIK3CA was significantly correlated to the gene copy number in nine HNSCC cell lines. In addition, the expression level of SCCRO and PIK3CA was significantly greater in malignant tissues compared with those in histologically normal mucosae (2.17- and 2.46-fold, respectively; P < 0.001). Matched tumor normal control analysis revealed that 24.5 and 69.4% of patients expressed high levels of SCCRO and PIK3CA, respectively. Univariate analyses demonstrated that SCCRO overexpression correlated with nodal metastases (P = 0.05) and advanced stage (P = 0.02), whereas PIK3CA overexpression was associated with vascular invasion (P = 0.04). Only SCCRO overexpression was associated with disease-specific (P = 0.04) and overall survival (P = 0.02). Furthermore, SCCRO overexpression remained an independent predictor for cervical nodal metastasis on multivariate regression analysis (chi(2) likelihood ratio = 4.38; P = 0.04). CONCLUSIONS: Although both SCCRO and PIK3CA may play a role in the pathogenesis of oral tongue SCC through amplification at 3q26, SCCRO appears to be a significant predictor of regional metastasis and may be a marker for tumor aggressiveness and clinical outcome.
PURPOSE: Amplification at chromosome 3q26.3 is a common and crucial event in head and neck squamous cell carcinoma (HNSCC), impacting significantly on tumor progression and clinical outcome. Two novel oncogenes, namely squamous cell carcinoma (SCC)-related oncogene (SCCRO) and PIK3CA (gene encoding phosphatidylinositol-3 kinase catalytic alpha-polypeptide), have been identified as targets of 3q26.3 amplification. This study aimed to delineate the role of SCCRO and PIK3CA in the pathogenesis of oral tongue SCC. EXPERIMENTAL DESIGN: The association between gene copy number for SCCRO and PIK3CA measured by fluorescence in situ hybridization and level of mRNA expression quantitated by real-time reverse transcription-PCR was assessed in a panel of human HNSCC cell lines. In addition, gene expression in 49 consecutive primary SCCs of the oral tongue was determined and correlated with clinicopathological characteristics and outcome. RESULTS: The mRNA level of SCCRO and PIK3CA was significantly correlated to the gene copy number in nine HNSCC cell lines. In addition, the expression level of SCCRO and PIK3CA was significantly greater in malignant tissues compared with those in histologically normal mucosae (2.17- and 2.46-fold, respectively; P < 0.001). Matched tumor normal control analysis revealed that 24.5 and 69.4% of patients expressed high levels of SCCRO and PIK3CA, respectively. Univariate analyses demonstrated that SCCRO overexpression correlated with nodal metastases (P = 0.05) and advanced stage (P = 0.02), whereas PIK3CA overexpression was associated with vascular invasion (P = 0.04). Only SCCRO overexpression was associated with disease-specific (P = 0.04) and overall survival (P = 0.02). Furthermore, SCCRO overexpression remained an independent predictor for cervical nodal metastasis on multivariate regression analysis (chi(2) likelihood ratio = 4.38; P = 0.04). CONCLUSIONS: Although both SCCRO and PIK3CA may play a role in the pathogenesis of oral tongue SCC through amplification at 3q26, SCCRO appears to be a significant predictor of regional metastasis and may be a marker for tumor aggressiveness and clinical outcome.
Authors: Verena L Bauer; Herbert Braselmann; Michael Henke; Dominik Mattern; Axel Walch; Kristian Unger; Michael Baudis; Silke Lassmann; Reinhard Huber; Johannes Wienberg; Martin Werner; Horst F Zitzelsberger Journal: J Mol Med (Berl) Date: 2008-09-23 Impact factor: 4.599
Authors: Karl C Bruckman; Frank Schönleben; Wanglong Qiu; Victoria L Woo; Gloria H Su Journal: Oral Surg Oral Med Oral Pathol Oral Radiol Endod Date: 2010-09-01
Authors: Jared T Hammill; Daniel C Scott; Jaeki Min; Michele C Connelly; Gloria Holbrook; Fangyi Zhu; Amy Matheny; Lei Yang; Bhuvanesh Singh; Brenda A Schulman; R Kiplin Guy Journal: J Med Chem Date: 2018-03-26 Impact factor: 7.446
Authors: Jared T Hammill; Deepak Bhasin; Daniel C Scott; Jaeki Min; Yizhe Chen; Yan Lu; Lei Yang; Ho Shin Kim; Michele C Connelly; Courtney Hammill; Gloria Holbrook; Cynthia Jeffries; Bhuvanesh Singh; Brenda A Schulman; R Kiplin Guy Journal: J Med Chem Date: 2018-03-26 Impact factor: 7.446
Authors: Wanglong Qiu; Frank Schönleben; Xiaojun Li; Daniel J Ho; Lanny G Close; Spiros Manolidis; Boyce P Bennett; Gloria H Su Journal: Clin Cancer Res Date: 2006-03-01 Impact factor: 12.531
Authors: Ryan T Anderson; Stephen B Keysar; Daniel W Bowles; Magdalena J Glogowska; David P Astling; J Jason Morton; Phuong Le; Adrian Umpierrez; Justin Eagles-Soukup; Gregory N Gan; Brian W Vogler; Daniel Sehrt; Sarah M Takimoto; Dara L Aisner; Francois Wilhelm; Barbara A Frederick; Marileila Varella-Garcia; Aik-Choon Tan; Antonio Jimeno Journal: Mol Cancer Ther Date: 2013-07-19 Impact factor: 6.261