Aneuploidy in Hepatocellular Carcinoma: Risk factors, mechanisms, and clinical relevance

Mechanisms of aneuploidy set the stage for cancer. Aneuploidy, an aberration in chromosome number in a cell, occurs naturally during cellular development in certain tissues. However, aneuploidy is omnipresent in cancer as cancer cells express complex karyotypes with chromosome numbers that deviate from the norm. Aneuploidy is a hallmark in Hepatocellular Carcinoma (HCC), as it is linked to poor prognosis due to genetic and epigenetic aberrations. Mechanisms contributing to aneuploidy in HCC include chromosomal instability, telomere shortening, which promotes genomic instability in early tumor development, and telomere stabilization, which enhances tumor cell survival by preventing excessive telomere attrition in later stages. Multiple chromosomal alterations are linked to the progression of invasive tumors in HCC. Therefore, understanding the association between aneuploidy and HCC is critical because it could unravel the role of genetic and molecular alterations in HCC. This review sheds light on the risk factors associated with aneuploidy in HCC to aid the development of future therapeutic and diagnostic approaches for management of HCC.