Abstract

Dear Editor: Cancer is a complex genetic disease which gradually progresses in relation to the downregulated expression of tumor suppressor genes (TSGs). Inactivation of TSGs has been known to contribute to the abnormal proliferation, transformation, and progression in human cancers. It has been widely demonstrated that both the genetic and epigenetic events, together, play a crucial role in tumor progression. Epigenetic is defined as the heritable changes in gene expression that are not caused by alterations in the DNA sequence. Several studies have demonstrated the epigenetic alterations in colorectal carcinoma. Colorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer death in women and men in the USA. In contrast, the frequency of colorectal carcinoma is less in India. However, 20,159 cases of CRC among men and 16,317 cases among women were reported in India. The 14,134 and 11,556 mortality due to CRC was reported among men and women, respectively, in India. Most of the CRC cases originate from adenomas. The malignant potential of adenomas increases with size, grade of dysplasia, and degree of villous components, along with the number and order of genetic and epigenetic aberrations. Previous studies have also highlighted the hypermethylation in several TSGs in colorectal carcinoma. Recent reports suggest that PTEN has an important tumor suppressor role in colorectal carcinogenesis. However, more attentive study is needed to explore the association of PTEN loss with CRC development. PTEN, a tumor suppressor gene, has been recently isolated from chromosome 10q23.3. The involvement of PTEN promoter methylation has been reported in breast cancer, cervical cancer, endometrial cancer, colorectal cancer, and glioblastoma. However, no such study has been made to evaluate the role of the PTEN tumor suppressor gene in colorectal cancer in colorectal cancer in Indian population. The correlation of the progression of disease with that of the promoter hypermethylation seems to be an interesting phenomenon. Therefore, we aimed to analyze the PTEN gene promoter methylation in fresh colorectal cancer tissues and their adjacent normal tissues along with the colorectal metastases specimens and also to evaluate the association of PTEN hypermethylation with CRC progression. The major outcome of the study is that the PTEN hypermethylation is a frequent event in sporadic CRCs and colorectal metastases in the patients from Indian population. Promoter methylation of PTEN gene was determined by methylationspecific PCR. We also performed chi-square test to correlate the PTEN hypermethylation with the clinicobiological parameters of colorectal cancer and metastases specimens in order to evaluate the role of PTEN hypermethylation with the disease progression. Of the CRC specimens, 114 (51 %) have shown PTEN hypermethylation among the total of 223 CRC specimens. Thirty-eight specimens have been characterized as metastatic among 223 specimens. Thirty-one (82 %) specimens out of 38 colorectal metastases samples have also demonstrated PTEN hypermethylation. We would like to highlight the high rate of hypermethylation in advanced stage colorectal tumors than early stages of colorectal tumors. To examine the M. M. A. Rizvi (*) :A. Ali : S. J. Mehdi Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, Maulana Mohammad Ali Jauhar Marg, New Delhi 110025, India e-mail: rizvijmi@gmail.com

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