Genetic Landscape and Biomarkers of Hepatocellular Carcinoma.
By J. Zucman‐Rossi, A. Villanueva, J. Nault, J. Llovet. Gastroenterology, 2015
1,184 citations recorded by the source corpus.
Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer-related death. Its mortality has increased in Western populations, with a minority of patients diagnosed at early stages, when curative treatments are feasible. Only the multikinase inhibitor sorafenib is available for the management of advanced cases. During the last 10 years, there has been a clear delineation of the landscape of genetic alterations in HCC, including high-level DNA amplifications in chromosome 6p21 (VEGFA) and 11q13 (FGF19/CNND1), as well as homozygous deletions in chromosome 9 (CDKN2A). The most frequent mutations affect TERT promoter (60%), associated with an increased telomerase expression. TERT promoter can also be affected by copy number variations and hepatitis B DNA insertions, and it can be found mutated in preneoplastic lesions. TP53 and CTNNB1 are the next most prevalent mutations, affecting 25%-30% of HCC patients, that, in addition to low-frequency mutated genes (eg, AXIN1, ARID2, ARID1A, TSC1/TSC2, RPS6KA3, KEAP1, MLL2), help define some of the core deregulated pathways in HCC. Conceptually, some of these changes behave as prototypic oncogenic addiction loops, being ideal biomarkers for specific therapeutic approaches. Data from genomic profiling enabled a proposal of HCC in 2 major molecular clusters (proliferation and nonproliferation), with differential enrichment in prognostic signatures, pathway activation and tumor phenotype. Translation of these discoveries into specific therapeutic decisions is an unmet medical need in this field.
Subfields: Cancer Research, Hepatology, Oncology
View Paper: https://www.semanticscholar.org/paper/5fa333c25a69e1c8e35ae9b5e32dec4c9d16642d
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In Cancer Research
In Hepatology
- J. Llovet
- V. Mazzaferro
- Alejandro Forner1 , 2
- Peter R. Galle
- F. Piscaglia
- J. Raoul
- Robert F. Schwabe
- V. Vilgrain
In Oncology
Citations in the corpus
- Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma (2017, neutral): “Initiation and progression of HCC is considered a multi-step process, but the precise molecular events that underlie HCC formation remain only partially understood (Zucman-Rossi et al., 2015).”
- The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer (2016, background): “Of note, the β-catenin, Hippo, and PTEN pathways are important contributors to hepatocarcinogenesis (16, 134, 135).”
- EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. (2018, background): “Molecular subclasses of hepatocellular carcinoma (HCC) have been proposed as proliferation/non-proliferation, and the key drivers of this cancer have been identified after sequencing more than 1,500 samples in several studies.(562) The most prominent drivers (TERT, CTNNB1 and TP53) are cur-”