Identification of molecular markers for pancreatic adenocarcinoma diagnosis and prognosis.

Abstract

Pancreatic cancer is responsible for 2% of all types of diagnosed cancers in Brazil and the only curative treatment available is the surgical removal of the tumor in early stages of the disease. Prevention, early detection and treatment are poor, facing serious problems and asking for new identification methods for disease diagnosis and prognosis. While somatic mutation of some genes (KRAS2, CDKN2A, TP53 e SMAD4) is frequently found in pancreatic adenocarcinoma, recent studies have revealed a great mutational heterogeneity in these tumors, arguing for the necessity of extensive analyses to identify additional somatic mutations that could be clinically useful. The present project aims to analyze the transcriptome and exome (DNA) of pancreatic surgical samples of different malignant grades using Next Generation Sequencing (NGS) to identify transcriptional and somatic alterations associated with malignant transformation and progression of pancreatic ductal adenocarcinomas (PDAC). We will catalog and compare the expression of protein-coding and non-coding RNAs in fragments of PDAC, precursor lesions (intraepithelial neoplasias, PanINs) and non-tumor tissue isolated from the same tumor. After the optimization of methods to analyze in genomic scale pancreatic samples obtained through endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA), we will employ NGS to catalog and search for prevalent point somatic mutations in the exome of PDAC and mucinous cystic tumors. Identified candidates will be tested on a RNA/DNA sample panel from pancreatic tissue, cystic fluid and blood of patients with PDAC and precursor lesions to evaluate its potential use on early diagnosis and/or prediction of clinical evolution of the disease.