Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India.
Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha 751016, India.
Oral Oncol. 2017 Oct;73:27-35. doi: 10.1016/j.oraloncology.2017.07.030. Epub 2017 Aug 9.
CDKN2A/p16 is a known tumor suppressor gene with a homologous deletion in Oral Squamous cell carcinoma. CDKN2A/p16 is found to be inactivated in a broad spectrum of solid tumors and in more than 80% of OSCC. Molecular alteration of CDKN2A/p16 in progression of OSCC can pose an important tool for the prognosis of squamous cell carcinoma.
Systematic network analysis was carried out to obtain involvement of CDKN2A/p16 in oral cancer by polysearch and FunDO. In the present study we have screened 104 OSCC patients from eastern region of India for CDKN2A/p16 expression in recurrent and non-recurrent OSCC. The observation was validated by Comparative Genomic Hybridisation and Next generation sequencing in recurrent cases.
Systematic analysis revealed direct involvement of CDKN2A/p16 in oral cancer. There was a consistent downregulated expression of CDKN2A/p16 in the recurrent cases. The gene expression study confirmed a >5-fold downregulation of CDKN2A/p16 in recurrent tumors as compared to non-recurrent ones. Array CGH analysis revealed a copy number deletion in the recurrent case. Furthermore, next generation sequencing validated deletion of CDKN2A/p16 and reported it asa common variant with a nonsense mutation having stop /loss of function of the gene in recurrent cases. Recurrent cases with deleted CDKN2A/p16 expression had poor prognosis and low survival rate.
CDKN2A/p16 frequently alters in oral cancer progression with a deletion/loss of function in the recurrent cases displaying its role in aiding several molecular events for the malignant transformations occurring throughout disease progression.
CDKN2A/p16 是一种已知的肿瘤抑制基因，在口腔鳞状细胞癌中存在同源缺失。CDKN2A/p16 在广泛的实体瘤和超过 80%的 OSCC 中失活。CDKN2A/p16 在 OSCC 进展中的分子改变可以为鳞癌的预后提供重要工具。
通过 polysearch 和 FunDO 进行系统网络分析，获得 CDKN2A/p16 在口腔癌中的参与情况。在本研究中，我们筛选了来自印度东部地区的 104 例 OSCC 患者，以检测 CDKN2A/p16 在复发性和非复发性 OSCC 中的表达。通过比较基因组杂交和下一代测序对复发性病例进行了验证。
系统分析显示 CDKN2A/p16 直接参与口腔癌。复发性病例中 CDKN2A/p16 的表达持续下调。基因表达研究证实，与非复发性肿瘤相比，复发性肿瘤中 CDKN2A/p16 的表达下调了 5 倍以上。阵列 CGH 分析显示复发性病例存在拷贝数缺失。此外，下一代测序验证了 CDKN2A/p16 的缺失，并报告其为一种常见的变异，具有无义突变，导致基因失活/功能丧失，在复发性病例中。具有缺失 CDKN2A/p16 表达的复发性病例预后不良，生存率低。
CDKN2A/p16 在口腔癌进展中频繁改变，复发性病例缺失/功能丧失，显示其在促进疾病进展过程中发生的多种分子事件中的作用。
