Table 3 Examples of interesting observations in aneuploidy studies including some conflicting data.  Some comments are also offered to explain them

1. The dynamic relationship between aneuploidy and CIN

Aneuploidy generates CIN, including increased chromosome loss, mutation rate and defective DNA damage repair [39, 119].

The relationship between aneuploidy and CIN can be envisioned as a “vicious cycle,” wherein one potentiates the other [120].

The “stress–CIN–cancer evolution relationship” can also be used to discuss the relationship between aneuploidy and cancer [50].

Elevated transcriptome dynamics are linked to karyotype changes which impact multiple genetic/epigenetic interactions [121,122,123]

Aneuploidy is less influential compared to structure alterations [54].

CIN rates might be more predictive for tumor outcome than assessing aneuploidy rates alone [54, 124].

Many cancer cell lines with aneuploidy are relatively stable (an example of fuzzy inheritance of some relatively stable systems) [37].

Genome chaos, including karyoplast budding, giant cells and mitotic catastrophe, is often associated with aneuploidy [67, 125,126,127].

Chromosomal condensation defects (DMFs) and Chromosome fragmentation (C-Frags) can generate aneuploidy [37, 106, 118].

Aneuploidy (in the form of mosaicism) represents a common phenomenon. We may all have a touch of Down syndrome [128, 129].

Aneuploidy is a main feature among individual cancer cell lines. The rate of aneuploidy seems inherited [72].

Genomic PTEN deletion size influences the landscape of aneuploidy and outcome in prostate cancer [130].

ATM and p21 cooperate to suppress aneuploidy and tumor development [117]

2. The complex relationship between aneuploidy and immune response

When co-cultured with natural killer cells, aneuploidy cells with complex karyotype-induced senescent cells were selectively cleared [131].

High copy number alterations in melanoma patients are linked with less effective response to immune checkpoint blockade anti–CTLA-4 [52].

3. Biological impact of aneuploidy

Aneuploidy changes the genomic coding, which affects the transcriptome, proteome, network structure, incidence of CIN and phenotypes [4, 37, 132].

Chromosome mis-segregation per se can alter the genome in many ways in addition to chromosome gain or loss [133].

Aneuploidy puts pressure on the protein machinery and quality control, which generates a global stress response, reducing cell proliferation [133].

Both specific gene effects and the typical aneuploidy stress response contribute to new genomic coding or/and increased system stress, which can impact the emergent process of cancer evolution ([133], current paper)

Karyotype status (e.g. aneuploidy and polyploidy) can restore functions of specific genes (e.g. MYO1). Thus, genomic coding changes gene coding [83].

The chromosomal size involved in aneuploidy is inversely correlated to the resulting fitness [134].

The risk of cancers to metastasize is proportional to the degree of cancer-specific aneuploidy [48].

There is a dynamic relationship between epigenetic events and aneuploidy; epigenetic marks play a role in the control of chromosome segregation and integrity; aneuploidy impacts chromatin silencing [135,136,137].

New approaches are needed to study the complexity of systems, including that of aneuploidy-mediated karyotype evolution [138, 94, 110].