摘要
Hepatoblastoma(HB)is the most frequent pediatric primary liver tumor.When the tumoral lesions can be resected,prognosis is generally favorable.However,there is a significant number of cases in which resection is not possible at diagnosis,and patients usually receive neo-adjuvant cisplatin-based chemotherapy prior to surgery.Unfortunately,some HBs develop resistance to initial chemotherapy or after recurrence,progressing to metastatic disease.Moreover,long-term side effects of chemotherapy remain a serious concern.Understanding the molecular bases of HB development and progression is thus essential for the identification of more efficacious therapies.HBs have a very low mutational burden,and the most frequent mutations occur in the CTNN1B gene(>80%of cases)and to a lesser extent in NFE2L2(~10%of cases).These observations suggest that other pathogenic processes besides genetic mutations may play a role in HB tumorigenesis.Epigenetic mechanisms encompass a variety of molecular processes with a tremendous potential to regulate gene expression.They include the covalent modifications of DNA and histones,the activity of enzymatic chromatin remodelers,and the expression of non-coding RNAs.Dysregulation of epigenetic processes has clearly become a hallmark of cancer.Regarding HB,recent studies have explored its epigenetic landscape,the expression of specific epigenetic effectors,and the tumorigenic consequences of epigenetic alterations.The reversible nature of most epigenetic modifications and the possibility to target non-coding RNAs may pave the way for new therapeutic avenues in HB.Here,we summarize and discuss the most relevant findings in this less explored aspect of HB.
基金
CIBERehd
grant PI19/00163 from Instituto de Salud CarlosⅢ(ISCⅢ)co-financed by“Fondo Europeo de Desarrollo Regional”(FEDER)“Una manera de hacer Europa”
grants PID2019-104878RB-100/AEI/10.13039/501100011033 and PID2019-104265RB-100/AEI/10.13039/501100011033,from FEDER/Ministerio de Ciencia,Innovación y Universidades-Agencia Estatal de Investigación
AECC LAB 2020 project:Novel epigenetic approaches for the treatment of hepatic and digestive cancers,from Spanish Association Against Cancer(AECC)
Fundación Eugenio Rodríguez Pascual
Fundación Mario Losantos,Fundación M.Torres
POSTD18014AREC post-doctoral fellowship from AECC to MA,and Ramón y Cajal Program contract RYC-2018-024475-1 to MGFB
FIMA-AC predoctoral fellowship to AC-C.The generous support of Mr.Eduardo Avila is acknowledged.
