Journal Article

A Peculiar Mutation Spectrum Emerging from Young Peruvian Patients with Hepatocellular Carcinoma

Ruiz, Eloy, Deharo, Eric, Marchio, Agnès, Rojas Rojas, Teresa, Pineau, Pascal, Doimi, Franco, Dejean, Anne, Bertani, Stéphane, Terris, Benoît

2014

Overview

Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abdomen / Adult / Age / Aged / Aged, 80 and over / Analysis / Biology and Life Sciences / Cancer / Carcinogenesis / Carcinogens / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - pathology / Cell cycle / Cell growth / Contact inhibition / DNA Mutational Analysis / Epidemiology / Female / Gene Expression Regulation, Neoplastic / Gene sequencing / Genetic aspects / Genetics / Glycoproteins / Hepatitis / Hepatocellular carcinoma / Historical account / Humans / Kinases / Life Sciences / Liver / Liver cancer / Liver diseases / Liver Neoplasms - genetics / Liver Neoplasms - pathology / Male / Medicine and Health Sciences / Middle Aged / Mutation / Mutation hot spots / Neoplasm Proteins - biosynthesis / Neoplasm Proteins - genetics / Neoplasms / p53 Protein / Patients / People and Places / Peru / Public health / Signal transduction / Signal Transduction - genetics / Southern Hemisphere / Spectrum analysis / Stem cells / Transcription / Transcription factors / Tumor proteins / Tumors / Young adults / α-Fetoprotein