Chromosomal breaks: another differential gap between early-onset and late-onset colorectal cancers.

Abstract

[EN] Colorectal cancer remains the second most common cause of cancer-related death in Western countries in terms of incidence and mortality, and is the most common tumour type in both sexes1. Up to 10% of all patients with colorectal cancer are younger than 50 years at diagnosis, and the incidence of early-onset colorectal cancer (EOCRC) has increased in recent decades2. Several approaches have been used to elucidate the molecular basis of EOCRC. One of these involves its comparison with late-onset colorectal cancer (LOCRC), as the two colorectal cancer types show differential profiles3–8.

Cumulative genomic alterations can lead to the development of cancer, which is caused by genomic aberrations that drive tumour initiation and progression. Oncogene activation and tumour suppressor gene inactivation can be caused by several types of somatic DNA aberrations, one of which is the structural variant9. Such aberrations can involve deletions, insertions, and inversions, as well as intrachromosomal and interchromosomal translocations, all of which produce chromosomal breaks10. These types of genetic alteration and their consequent effects have rarely been analysed. A recent study11 showed that chromosomal breaks associated with copy number alterations occurring within genes represent a highly prevalent and clinically relevant subset of structural variants in colorectal cancer, with prevalence rates comparable to those of gene point mutations, and lead to stratified prognostic impacts in colorectal cancer.