Genomic Instability and Hepatocellular Carcinoma
A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".
Deadline for manuscript submissions: closed (20 November 2020) | Viewed by 290
Special Issue Editor
Institute of Human Genetics, Medical School Hannover, Hannover, Germany
Interests: chromosomal instability in solid tumors; Hepatocellular carcinoma; Cholangiocellular carcinoma
Special Issue Information
Dear Colleagues,
HCC is known as the sixth most commonly cancer diagnosed worldwide and the fourth cancer most frequently leading to death. Hepatitis B and C, uptake of aflatoxins and alcohol, and diabetes are discussed as major risk factors leading to the development of HCC. Ongoing processes of destruction and remodelling of damaged liver tissue lead to cirrhosis of this organ, and are involved in the development of HCC. Regenerative and dysplastic nodules are observed as part of a sequence that results in HCC. The development of HCC, in particular, when occurring as a histologically high-grade tumour, is often accompanied by genomic instability (GI), for example, as chromosomal instability (CIN), microsatellite instability (MSI), and/or CpG island methylator phenotype (CIMP).
Whereas MSI and CIMP are known by most oncologists due to therapeutic implications based on these types of GI, CIN remains outside this focus. CIN is defined as an increase in the number of structural and/or numerical imbalances in a single tumour cell and/or tumour cell population. CIN, as also seen for MSI and CIMP, occurs in the majority of carcinomas. It is associated with cellular transformation, inter- and intratumoural heterogeneity, tumour progression, metastasis, and drug resistance. Not surprisingly, CIN is associated with a generally worse patient outcome. While low to moderate degrees of CIN have been discussed as a driving mechanism of cancer development, higher grades of CIN seem to lower the viability of tumour cells as seen, e.g., for oestrogen-negative breast cancer. MSI and CIMP, on the other hand, are defined molecular processes based on failure of a number of genes responsible for DNA repair and methylation of promoter genes important for cell growth and DNA integrity.
Despite the obvious importance of these mechanisms of GI for cancer development, the basic molecular mechanisms are still poorly understood. As an example, nearly 2300 genes are assumed to be important in CIN, but less than 150 genes are already identified as important. Most of these genes are involved in the development and function of spindle assembly, kinetochore function, DNA repair/replication, and chromatid aggregation/segregation.
Further efforts are therefore necessary to overcome this gap in our knowledge of these types of GI. This Special Issue will therefore focus on GI in regard to the abovementioned aspects, in particular, in regard to HCC. New attempts to foster understanding will be described, in addition to providing an overview of this interesting field of research.
Prof. Dr. Ludwig Wilkens
Guest Editor
Manuscript Submission Information
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Keywords
- hepatocellular carcinoma
- genomic instability
- chromosomal instability
- pathway
- chromosomal imbalances
- gene expression
- array
