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Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry

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dc.contributor.author Cerapio, Juan Pablo es_PE
dc.contributor.author Marchio, Agnès es_PE
dc.contributor.author Cano, Luis es_PE
dc.contributor.author López, Ignacio es_PE
dc.contributor.author Fournié, Jean-Jacques es_PE
dc.contributor.author Régnault, Béatrice es_PE
dc.contributor.author Casavilca-Zambrano, Sandro es_PE
dc.contributor.author Ruiz, Eloy es_PE
dc.contributor.author Dejean, Anne es_PE
dc.contributor.author Bertani, Stéphane es_PE
dc.contributor.author Pineau, Pascal es_PE
dc.date.accessioned 2024-05-30T23:13:38Z
dc.date.available 2024-05-30T23:13:38Z
dc.date.issued 2021
dc.description This work was supported by the Alliance pour les Sciences de la Vie et de la Santé (AVIESAN), ITMO Cancer ENV201408 (to S.B.) and the Ligue Contre le Cancer (to P.P.). J.P.C. was a recipient of a doctoral scholarship from the Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT) 212-2015-FONDECYT and was supported by a fellowship from Campus France 941211E; L.C. was supported by a doctoral fellowship from IRD ARTS-2016-878573B; I.L. was supported by a postdoctoral fellowship from the Fondation ARC pour la Recherche sur le Cancer PDF20170505624; J.J.F. has received funding from the Agence Nationale de la Recherche (ANR) under the Investments for the Future program 11-LABX-0068; S.C.Z. and E.R. have received funding from the World Bank Group and FONDECYT-CONCYTEC under the Research Infrastructure Improvement program 016-2018-FONDECYT/BM; and S.B. has received funding from the European Union’s Horizon 2020 Framework program under the Marie Skłodowska-Curie Actions 823935.
dc.description.abstract Hepatocellular carcinoma (HCC) usually afflicts individuals in their maturity after a protracted liver disease. Contrasting with this pattern, the age structure of HCC in Andean people displays a bimodal distribution with half of the patients developing HCC in adolescence and early adulthood. To deepen our understanding of the molecular determinants of the disease in this population, we conducted an integrative analysis of gene expression and DNA methylation in HCC developed by 74 Peruvian patients, including 39 adolescents and young adults. While genome-wide hypomethylation is considered as a paradigm in human HCCs, our analysis revealed that Peruvian tumors are associated with a global DNA hypermethylation. Moreover, pathway enrichment analysis of transcriptome data characterized an original combination of signatures. Peruvian HCC forgoes canonical activations of IGF2, Notch, Ras/MAPK, and TGF-β signals to depend instead on Hippo/YAP1, MYC, and Wnt/β-catenin pathways. These signatures delineate a homogeneous subtype of liver tumors at the interface of the proliferative and non-proliferative classes of HCCs. Remarkably, the development of this HCC subtype occurs in patients with one of the four Native American mitochondrial haplogroups A-D. Finally, integrative characterization revealed that Peruvian HCC is apparently controlled by the PRC2 complex that mediates cell reprogramming with massive DNA methylation modulating gene expression and pinpointed retinoid signaling as a potential target for epigenetic therapy. © 2021 Cerapio et al.
dc.description.sponsorship Fondo Nacional de Desarrollo Científico y Tecnológico - Fondecyt
dc.identifier.doi https://doi.org/10.18632/oncotarget.27890
dc.identifier.scopus 2-s2.0-85103237314
dc.identifier.uri https://hdl.handle.net/20.500.12390/2373
dc.language.iso eng
dc.publisher Impact Journals LLC
dc.relation.ispartof Oncotarget
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/3.0/
dc.subject Liver cancer
dc.subject Hepatitis B virus es_PE
dc.subject Indigenous people es_PE
dc.subject Integrative genomics es_PE
dc.subject.ocde http://purl.org/pe-repo/ocde/ford#3.04.03
dc.title Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry
dc.type info:eu-repo/semantics/article
dspace.entity.type Publication
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