Why cancer chromosome disorder can thrive

The research results were published in the issue of the European Molecular Biology Organization (European Molecular Biology Organization) on October 26, 2021

Cancer is driven by many types of genetic changes, including DNA mutations and copy number changes, ranging from small insertions and deletions to entire genome replication events

In general, somatic cell copy number changes in tumors often lead to abnormal chromosome numbers, called aneuploidy, which has been shown to promote tumor development by increasing genetic diversity, instability and evolution

In recent years, it is obvious that cells coexisting in the tumor microenvironment are not only affected by external stressors (mainly metabolic sources, such as nutritional deficiencies), but also by internal stressors aneuploidy

When this main transport/export system is disrupted, the general immune response attempts to restore normal function by stopping the accumulation, degradation and removal of misfolded proteins (UPR) and activating signaling pathways to promote proper protein folding

If homeostasis cannot be quickly restored, non-tumor cells will die

"In these cases, they will also draw neighboring cells in a spiral of deception and gradually damage local immune cells," said senior co-author Maurizio Zanetti, MD, a professor of medicine at the University of California San Diego School of Medicine and Morse Cancer Center.

The researchers hypothesized that aneuploidy, general immune response, and immune cell disorders may be linked in a fatal triangle

"This is an unprecedentedly ambitious goal," Hannah Carter said

"We know this task is challenging," Carter added.

They said these findings indicate that the stress response in cancer cells acts as an unpredictable link between aneuploidy and immune cells, thereby "reducing immunity and anti-tumor effects

The authors say that these findings provide new opportunities for understanding tumor progression.

They said that in practice, a new aneuploidy score developed for this study defines the burden of chromosomal abnormalities, which can establish a new paradigm for assessing the biological stage of a patient’s tumor progression and be used to infer immune status.

"It may also provide new opportunities for pharmacological or genetic intervention, interfere with specific branches of the universal periodic review, and act as an intermediary for aneuploidy-driven local immune disorders

1. Su Xian, Magalie Dosset, Gonzalo Almanza, Stephen Searles, Paras Sahani, T Cameron Waller, Kristen Jepsen, Hannah Carter, Maurizio Zanetti.

   
   

2. Maurizio Zanetti.

   
   

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