However, the theory of Boveri was forgotten until the molecular biologist Peter Duesberg reappraised it. Understanding through what mechanisms it can affect tumor evolution is an important topic of current cancer research.Somatic mosaicism occurs in virtually all cancer cells, including trisomy 12 in chronic lymphocytic leukemia (CLL) and trisomy 8 in acute myeloid leukemia (AML). However, these forms of mosaic aneuploidy occur through mechanisms distinct from those typically associated with genetic syndromes involving complete or mosaic aneuploidy, such as chromosomal instability (due to mitotic segregation defects in cancer cells). Therefore, the molecular processes that lead to aneuploidy are targets for the development of cancer drugs. Both resveratrol and aspirin have been found in vivo (in mice) to selectively destroy tetraploid cells that may be precursors of aneuploid cells, and activate AMPK, which may be involved in the process.Alteration of normal mitotic checkpoints are also important tumorigenic events, and these may directly lead to aneuploidy. Loss of tumor suppressor p53 gene often results in genomic instability, which could lead to the aneuploidy genotype.In addition, genetic syndromes in which an individual is predisposed to breakage of chromosomes (chromosome instability syndromes) are frequently associated with increased risk for various types of cancer, thus highlighting the role of somatic aneuploidy in carcinogenesis.The ability to evade the immune system appears to be enhanced in tumoral cells with strong aneuploidy. This has therefore suggested that the presence of an abnormal number of chromosomes might be an effective predictive biomarker for response to precise immunotherapy.
A third daughter cell may end up with the missing chromosome. Multipolar spindles: more than two spindle poles form. Such a mitotic division would result in one daughter cell for each spindle pole; each cell may possess an unpredictable complement of chromosomes. Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled. A tetraploid intermediate may be produced as the end-result of the monopolar spindle mechanism. In such a case, the cell has double the copy number of a normal cell, and produces double the number of spindle poles as well. This results in four daughter cells with an unpredictable complement of chromosomes, but in the normal copy number. Somatic mosaicism in the nervous system
Mosaicism for aneuploid chromosome content may be part of the constitutional make-up of the mammalian brain. In the normal human brain, brain samples from six individuals ranging from 2–86 years of age had mosaicism for chromosome 21 aneuploidy (average of 4% of neurons analyzed). This low-level aneuploidy appears to arise from chromosomal segregation defects during cell division in neuronal precursor cells, and neurons containing such aneuploid chromosome content reportedly integrate into normal circuits. However, recent research using single-cell sequencing has challenged these findings, and has suggested that aneuploidy in the brain is actually very rare. Somatic mosaicism in cancer
Aneuploidy is consistently observed in virtually all cancers. The German biologist Theodor Boveri was first to propose a causative role for aneuploidy in cancer.