@article{fdi:010082444,
  title = {{G}lobal {DNA} hypermethylation pattern and unique gene expression signature in liver cancer from patients with {I}ndigenous {A}merican ancestry},
  author = {{C}erapio, {J}.{P}. and {M}archio, {A}. and {C}ano, {L}. and {L}ópez, {I}. and {F}ourni{\'e}, {J}.{J}. and {R}{\'e}gnault, {B}. and {C}asavilca-{Z}ambrano, {S}. and {R}uiz, {E}. and {D}ejean, {A}. and {B}ertani, {S}t{\'e}phane and {P}ineau, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{H}epatocellular carcinoma ({HCC}) usually afflicts individuals in their maturity after a protracted liver disease. {C}ontrasting with this pattern, the age structure of {HCC} in {A}ndean people displays a bimodal distribution with half of the patients developing {HCC} in adolescence and early adulthood. {T}o 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 {P}eruvian patients, including 39 adolescents and young adults. {W}hile genome-wide hypomethylation is considered as a paradigm in human {HCC}s, our analysis revealed that {P}eruvian tumors are associated with a global {DNA} hypermethylation. {M}oreover, pathway enrichment analysis of transcriptome data characterized an original combination of signatures. {P}eruvian {HCC} forgoes canonical activations of {IGF}2, {N}otch, {R}as/{MAPK}, and {TGF}-? signals to depend instead on {H}ippo/{YAP}1, {MYC}, and {W}nt/?-catenin pathways. {T}hese signatures delineate a homogeneous subtype of liver tumors at the interface of the proliferative and non-proliferative classes of {HCC}s. {R}emarkably, the development of this {HCC} subtype occurs in patients with one of the four {N}ative {A}merican mitochondrial haplogroups {A}-{D}. {F}inally, integrative characterization revealed that {P}eruvian {HCC} is apparently controlled by the {PRC}2 complex that mediates cell reprogramming with massive {DNA} methylation modulating gene expression and pinpointed retinoid signaling as a potential target for epigenetic therapy.},
  keywords = {{PEROU}},
  booktitle = {},
  journal = {{O}ncotarget},
  volume = {12},
  numero = {5},
  pages = {475--492},
  ISSN = {1949-2553},
  year = {2021},
  DOI = {10.18632/oncotarget.27890},
  URL = {https://www.documentation.ird.fr/hor/fdi:010082444},
}