Epigenetic Alterations in Pancreatic Cancer

Jiaqi Shi*

Epigenetic Alterations in Pancreatic Cancer.

Pancreatic cancer is the fourth leading cause of cancer death and is predicted to be the second leading cause in a decade in the US. Despite more than 50 years of research and therapeutic development, pancreatic cancer still has a median survival rate of 6 months and a 5-year overall survival around 5%.

Therefore, there is an urgent need to better understand the mechanism of pancreatic cancer development, as well as to discover new biomarkers for early
diagnosis, prognosis, and therapeutic targets.

Recent whole genomic sequencing and copy number analysis of pancreatic ductal adenocarcinoma discovered many altered signaling pathways. Most of the studies have been focused on genetic abnormalities of driver mutations that occur in more than 50% of the pancreatic cancer cases, such as KRAS, TP53, SMAD4, and CDKN2A.

The other lower prevalence mutated genes include those involved in Deoxyribonucleic acid damage repair, chromatin remodeling, WNT signaling, Transforming Growth Factor beta signaling, Hedgehog signaling, and cell cycle regulation pathways. Recently it also became evident that many genetic alterations in pancreatic cancer target epigenetic regulators.

Epigenetics is the heritable alterations of gene expression without changing DNA sequence. DNA methylation, histone modification, and non-coding Ribonucleic acids are the most important mechanisms of epigenetic regulations.

These modifications alter chromatin structure and promoter accessibility, and thus lead to altered gene transcription. Recent studies showed that epigenetic alterations in cancer cells contribute to tumor initiation, progression, and metastasis. Whole genome sequencing studies revealed driver mutations in epigenetic regulators in human cancers. Some of the mutations are oncogenic, and other mutations are tumor suppressive.

Pancreas Open J. 2016; 1(2): e5-e7. doi: 10.17140/POJ-1-e002