title: A peculiar mutation spectrum emerging from young peruvian patients with hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Institut Pasteur, Unité Organisation Nucléaire et Oncogenèse, Paris, France; INSERM, U993, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Marchio
authors.affiliation: Université de Toulouse, UPS, UMR152 PHARMADEV, Université Toulouse 3, Toulouse, France; Institut de Recherche pour le Développement, UMR152 PHARMADEV, Lima, Peru.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bertani
authors.affiliation: Aix-Marseille Université, UMR912 SESSTIM INSERM-IRD-AMU, Centre d'Epidémiologie et de Santé Publique des Armées, Marseille, France.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rojas Rojas
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas, Departamento de Patología, Banco de Tejidos Tumorales, Lima, Peru.
authors.forename: Franco
authors.initials: F
authors.lastname: Doimi
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service d'Anatomie et Cytologie Pathologiques, Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Terris
authors.affiliation: Université de Toulouse, UPS, UMR152 PHARMADEV, Université Toulouse 3, Toulouse, France; Institut de Recherche pour le Développement, UMR152 PHARMADEV, Vientiane, Laos.
authors.forename: Eric
authors.initials: E
authors.lastname: Deharo
authors.affiliation: Institut Pasteur, Unité Organisation Nucléaire et Oncogenèse, Paris, France; INSERM, U993, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas, Departamento de Cirugía en Abdomen, Lima, Peru.
authors.forename: Eloy
authors.initials: E
authors.lastname: Ruiz
authors.affiliation: Institut Pasteur, Unité Organisation Nucléaire et Oncogenèse, Paris, France; INSERM, U993, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010568:Peru; D015398:Signal Transduction / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins