Genomic structural variations and their role in carcinogenesis

Abstract

Rearrangements of the genome known as structural variations (SVs) that amplify, delete or reorder chromosomal material are an important source of genomic diversity across humans. Nowadays, with the recent improvements of sequencing technologies, SVs are conceived as a hallmark of cancer, and the molecular mechanisms underlying their oncogenic potential are being uncovered. SVs can alter cancer-related gene expression by disrupting the gene sequence, inducing copy number variations or forming fusion genes. Recently, 3D-genome organization has been shown to play an important role in the regulation of gene expression and the formation of genomic rearrangements. Disrupting genome structural organization, mainly topologically associating domains (TADs), can also trigger the activation of oncogenes and the onset of cancer. This review provides general insights into the current knowledge on SVs, including their formation, their significance in carcinogenesis, state-of-the-art detection methods and their relevance in the clinic, highlighting their potential implementation in early diagnosis and personalized medicine.