Epigenetics Insight

**85**

**Chapter 5**

**Abstract**

microRNA, 3' UTR

**1. Introduction**

portion of patients [4].

**2. PDAC from genetics to epigenetics**

Epigenetics: Dissecting Gene

*Alia Abukiwan and Martin R. Berger*

Expression Alteration in PDAC

Pancreatic cancer is the fourth leading cause of cancer deaths, with a low 5-year survival rate of about 7% due to its highly invasive nature. Pancreatic ductal adenocarcinoma (PDAC) comprises more than 90% of all pancreatic cancer cases. At the time of detection, around 80% of cases harbor metastases due to the lack of early diagnosis. For decades, scientists have primarily focused on dissecting the origin of pancreatic cancer through genetic alterations and their contribution to diagnosis. Recently, PDAC research has turned into epigenetics to revolutionize our understanding about the silencing of critical regulatory genes. Epigenetic events can be divided mechanistically into various components, including DNA methylation, histone posttranslational modification, nucleosome remodeling, and regulation of transcription or translation by microRNA. The identified epigenetic processes in PDAC contribute to its specific epigenotype and are correlated phenotypic features. Strikingly, some of them have been suggested to have potential as cancer biomarkers, for disease monitoring, prognosis, and risk validation. As epigenetic aberrations are

reversible, their correction will become as a promising therapeutic target.

**Keywords:** PDAC, epigenetics, DNA methylation, histone modification,

Pancreatic ductal adenocarcinoma (PDAC) comprises more than 90% of all pancreatic cancer cases. It is highly aggressive, extremely lethal and shows resistance to chemotherapy [1–3]. At diagnosis, around 80% of PDAC cases have already metastasized, thus rendering the current therapeutic options practically ineffective. In line with this, potentially curative surgical resection is limited to a very small

On the other hand, cancer metastasis is associated not only with simple gene/ protein expression models but also with the existence of epigenetic mechanisms [5], which complicates this process through DNA methylation, histone modifications, and microRNA regulation (see **Figure 1**). Recent studies uncovered the regulatory mechanisms of each process and their key role in EMT and cancer metastasis [6].

Historically, the development of PDAC was attributed to DNA mutations, which are classified into three main types: oncogenes (KRAS, BRAF, AKT2, MYB, and AIBI),
