Rajendran Senthilnathan, Muthupalani Rajendran Shanmugam, Ramanathan Arvind
Department of Oral and Maxillofacial Surgery, Meenakshiammal Dental College and Hospital, Maduravoyal, India.
Asian Pac J Cancer Prev. 2013;14(2):1073-5. doi: 10.7314/apjcp.2013.14.2.1073.
In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected to ubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolled proliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in a functional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFR and promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung and hematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is not known. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samples for mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be most frequently mutated in other cancers.
Total genomic DNA isolated from thirty two post surgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for the RING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations.
The sequencing data of the thirty two OSCC samples did not identify mutations in the RING finger domain coding region of c-Cbl gene.
To the best of our knowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. The present data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in OSCC samples.
在正常细胞中,活化的表皮生长因子受体(EGFR)分子会通过c-Cbl(一种检查不受控制增殖的泛素连接酶)介导的泛素化蛋白酶体降解途径进行降解。因此,野生型c-Cbl分子的表达对于维持这种降解机制的功能状态至关重要。c-Cbl表达或功能的丧失可能会导致EGFR持续激活并促进癌变,c-Cbl基因的功能丧失突变已在肺癌和血液系统癌症中被报道。然而,c-Cbl在口腔鳞状细胞癌(OSCC)中的基因状态尚不清楚。因此,在本研究中,我们调查了从OSCC组织活检样本中分离的基因组DNA,以寻找c-Cbl基因编码环指结构域的区域中的突变,该区域在其他癌症中也被报道为最常发生突变的区域。
使用位于c-Cbl基因第8外显子两侧的引物对从32个手术后OSCC组织样本中分离的总基因组DNA进行扩增,该外显子编码环指结构域。然后将PCR扩增产物在1.2%琼脂糖凝胶中进行分离、纯化,并进行直接测序以筛选突变。
32个OSCC样本的测序数据未发现c-Cbl基因编码环指结构域的区域中有突变。
据我们所知,这是首次对OSCC样本中c-Cbl基因的基因状态进行研究。目前的数据表明,c-Cbl基因编码环指结构域的区域在OSCC样本中相对较少发生基因改变。