Identification and characterization of pancreatic cancer genes located within novel localized copy number alterations
Pancreatic cancer is perhaps the most lethal cancer afflicting mankind with incidence rate paralleling mortality rate in most populations. The highly invasive and metastatic nature of this cancer makes it refractory to conventional treatment regimens. We had earlier used array based comparative genomic hybridization and gene expression microarrays to identify novel copy number alterations in pancreatic cancer. Using a combination of cell and molecular biological approaches, we have commenced the characterization of two putative tumor suppressor genes located within novel homozygous deletions at 6q25 and 18q23. The deletion at 6q25 harbors ARID1B that encodes one of the two alternative DNA-binding components of the human SWI/SNF chromatin remodeling complex. The deletion at 18q23 harbors PARD6G that encodes a poorly studied subunit of the PAR complex. Current efforts are focused to unravel respective roles of the two genes in processes relevant to tumour progression including chromatin remodeling and cell motility.
Fig.1. Functional characterization of a novel pancreatic cancer tumor suppressor gene (TSG). Colony forming assay reveals a possible tumor suppressor role for a novel pancreatic cancer gene. Permanent transfectants generated in a pancreatic cancer cell line for the putative TSG form colonies that are less in number and size (panel A) than those generated from the vector alone (panel B). Panel C shows graphical representation of the result. Student’s t test p value is shown.