Genetic and epigenetic alterations in pancreatic carcinogenesis.

摘要: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in last decades, origin this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types pancreatic lesions can evolve towards cancer. These precursor include: intraepithelial neoplasia (PanIN) that are microscopic pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) Cystic (MCN) both macroscopic lesions. However, cellular these still a matter debate. Classically, neoplasm initiation or progression driven by several genetic epigenetic alterations. The aim review to assemble current information on mutations disorders affect genes during carcinogenesis. We will further discuss interest alterations for diagnosis prognosis PDAC. Large (chromosomal deletion/amplification) single point well described carcinogenesis inducers. Mutations classically occur within key regions genome. Consequences various include activation mitogenic pathways silencing apoptotic processes. Alterations K-RAS, P16 DPC4 frequently observed samples have been gradually DNA methylation an process involved imprinting X chromosome inactivation. Alteration patterns leads deregulation gene expression, absence mutation. Both events influence non-coding RNA with dramatic effects proliferation, survival invasion. Besides improvement our fundamental understanding development, highlighting molecular could provide new clinical tools early basis development effective therapies.