TO STUDY CHD-5 GENE POLYMORPHISM (4615T>C) IN PANCREATIC ADENOCARCINOMA PATIENTS AND PANCREATIC CANCER CELL LINES
Abstract
BACKGROUND: Chromodomain helicase DNA binding protein-5 gene (CHD-5) has been identified as tumor suppressor gene. Human chromosome 1p36 is a region consistently deleted in cancers. CHD-5 is located in this region. CHD-5 is the fifth member of a family of chromatin remodeling proteins. CHD-5 is preferentially expressed in the nervous system and testis. CHD-5 was first identified because of its location in a region of frequent deletion in neuroblastomas. Downregulation of CHD-5 gene expression has been observed in neuroblastoma, breast cancer, colon cancer and ovarian cancer etc. This may be explained by deletions or other mutations.
Pancreatic cancer is the 4th leading cause of cancer death. The most common type is pancreatic adenocarcinoma (PA), comprises about 90% of all the malignant neoplasms of pancreas. Chromodomain helicase DNA binding protein-5 gene (CHD-5) has been identified as tumor suppressor gene. Downregulation of CHD-5 gene expression has been observed in neuroblastoma, breast cancer, colon cancer and ovarian cancer etc. This may be explained by deletions or other mutations. A tumor-specific function-altering mutation is a well-established indicator for tumor suppressor genes in breast cancer and ovarian cancer etc. according to previous studies, but very less data is available about CHD-5 gene in pancreatic cancer. Here, CHD-5 gene polymorphism (4615T>C) has been studied in pancreatic adenocarcinoma and pancreatic cancer cell lines.
AIMS AND OBJECTIVES: To study CHD-5 gene polymorphism (4615 T>C) in histopathologically/ cytologically confirmed cases of PA and pancreatic cancer cell lines.
MATERIALS AND METHODS: This study was conducted in the Department of Biochemistry of MAMC, New Delhi. The blood sample of 20 patients of PA were taken along with 20 healthy controls. We evaluated CHD-5 gene polymorphism by using ASO-PCR after cell-free DNA extraction from plasma. We also did similar study in two pancreatic cancer cell lines: PANC-1 and MiaPaCa-2, after DNA extraction from cell lines followed by CHD-5 gene polymorphism by using ASO-PCR.
RESULTS AND CONCLUSION: SNP 4615T>C (Ser1539Pro) was present in 85% of cases as compared to 75% in controls. However, the difference was not significant. So, there was no association between SNP 4615T>C in CHD-5 gene and PA. SNP was present in PANC-1 but heterozygosity was seen in MIA PaCa-2 cell line.
Keywords: CHD-5 gene, Pancreatic adenocarcinoma, Single nucleotide Polymorphism
