Genetics of Hepatocellular Carcinoma: From Tumor to Circulating DNA

被引：24

作者：

Campani, Claudia ^{[1
,2
,3
]}

Zucman-Rossi, Jessica ^{[1
,2
,4
]}

Nault, Jean-Charles ^{[1
,2
,5
,6
]}

机构：

[1] Univ Paris Cite, Sorbonne Univ, Ctr Rech Cordeliers, Team Funct Genom Solid Tumors,Inserm, F-75006 Paris, France

[2] Equipe Labellisee Ligue Natl Canc, Labex OncoImmunol, F-75006 Paris, France

[3] Univ Firenze, Dept Expt & Clin Med, Internal Med & Hepatol Unit, I-50134 Florence, Italy

[4] Hop Europeen Georges Pompidou, AP HP, F-75015 Paris, France

[5] Hop Univ Paris Seine St Denis, AP HP, Hop Avicenne, Liver Unit, F-93000 Bobigny, France

[6] Univ Paris Nord, Unite Format & Rech St Med & Biol Humaine, F-93000 Bobigny, France

来源：

CANCERS | 2023年 / 15卷 / 03期

关键词：

hepatocellular carcinoma; genomics; target therapies; biomarkers; liquid biopsy; circulating tumor DNA; CELL-FREE DNA; MOLECULAR RESIDUAL DISEASE; LIVER-DISEASE; ACQUIRED-RESISTANCE; SOMATIC MUTATIONS; CLONAL EVOLUTION; HETEROGENEITY; CLASSIFICATION; BIOMARKER; VARIANT;

D O I：

10.3390/cancers15030817

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary In recent years, the genetic landscape of hepatocellular carcinoma (HCC) has been explored, identifying TERT promoter, CTNNB1, and TP53 as the most frequent mutated genes. Therapies directed against specific targetable genomic alterations are the basis of personalized medicine and represent the cornerstone of systemic treatment for many malignancies, but are not yet available in HCC. Tools such as liquid biopsy and, in particular, circulating tumor DNA (ctDNA) may help in identifying biomarkers of response or resistance to treatment, and their role in HCC is an active field of research. In this review, we summarize the available evidence on the HCC genomic landscape and the potential role of ctDNA in clinical practice. Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies and is one of the major causes of cancer-related death. Over the last 15 years, the molecular landscape of HCC has been deciphered, with the identification of the main driver genes of liver carcinogenesis that belong to six major biological pathways, such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase. The combination of genetic and transcriptomic data composed various HCC subclasses strongly related to risk factors, pathological features and prognosis. However, translation into clinical practice is not achieved, mainly because the most frequently mutated genes are undruggable. Moreover, the results derived from the analysis of a single tissue sample may not adequately catch the intra- and intertumor heterogeneity. The analysis of circulating tumor DNA (ctDNA) is broadly developed in other types of cancer for early diagnosis, prognosis and monitoring under systemic treatment in order to identify primary and secondary mechanisms of resistance. The aim of this review is to describe recent data about the HCC molecular landscape and to discuss how ctDNA could be used in the future for HCC detection and management.

引用

页数：19

共 119 条

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