Abstract IA12: Cancer evolution: Chromosomal instability and immune evasion

2022 ◽  
Author(s):  
Charles Swanton
Keyword(s):  
Immune Evasion ◽  
Chromosomal Instability ◽  
Cancer Evolution

scholarly journals Origins and Consequences of Chromosomal Instability: From Cellular Adaptation to Genome Chaos-Mediated System Survival

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1162 ◽  
Author(s):  
Christine J. Ye ◽  
Zachary Sharpe ◽  
Henry H. Heng
Keyword(s):  
Chromosomal Instability ◽  
Molecular Mechanisms ◽  
Evolutionary Model ◽  
Common Mechanism ◽  
Cancer Evolution ◽  
Two Phase ◽  
Cellular Adaptation ◽  
Somatic Evolution ◽  
New Research ◽  
Genome Chaos

When discussing chromosomal instability, most of the literature focuses on the characterization of individual molecular mechanisms. These studies search for genomic and environmental causes and consequences of chromosomal instability in cancer, aiming to identify key triggering factors useful to control chromosomal instability and apply this knowledge in the clinic. Since cancer is a phenomenon of new system emergence from normal tissue driven by somatic evolution, such studies should be done in the context of new genome system emergence during evolution. In this perspective, both the origin and key outcome of chromosomal instability are examined using the genome theory of cancer evolution. Specifically, chromosomal instability was linked to a spectrum of genomic and non-genomic variants, from epigenetic alterations to drastic genome chaos. These highly diverse factors were then unified by the evolutionary mechanism of cancer. Following identification of the hidden link between cellular adaptation (positive and essential) and its trade-off (unavoidable and negative) of chromosomal instability, why chromosomal instability is the main player in the macro-cellular evolution of cancer is briefly discussed. Finally, new research directions are suggested, including searching for a common mechanism of evolutionary phase transition, establishing chromosomal instability as an evolutionary biomarker, validating the new two-phase evolutionary model of cancer, and applying such a model to improve clinical outcomes and to understand the genome-defined mechanism of organismal evolution.

scholarly journals Chromosomal instability and aneuploidy: a conundrum in cancer evolution

2018 ◽  
Vol 1 ◽  
pp. 28-32
Author(s):  
Jasmin Ali
Keyword(s):  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Current Understanding ◽  
Cancer Therapies ◽  
Cancer Evolution ◽  
Hallmarks Of Cancer ◽  
Underlying Mechanisms ◽  
Merotelic Attachments

Chromosomal instability (CIN), defined as an increased rate of gain or loss of whole chromosomes, leads to aneuploid cells, which are cells that display an abnormal number of chromosomes. Both CIN and aneuploidy are hallmarks of cancer, yet the underlying mechanisms of CIN and aneuploidy and their impact on tumourigenesis have remained poorly defined. Although multiple mechanisms have been proposed to explain the role of CIN and aneuploidy in tumourigenesis, this review focuses on three principal pathways leading to CIN: spindle assembly checkpoint defects, merotelic attachments, and cohesion defects. Here, we provide a brief overview of the current understanding of the roles of these mechanisms in CIN and aneuploidy. We also present emerging evidence that contradicts the importance of certain mechanisms in cancer evolution. A clearer understanding of these fundamental pathways could prove to be helpful in developing effective cancer therapies.

PRC1: Linking Cytokinesis, Chromosomal Instability, and Cancer Evolution

2018 ◽  
Vol 4 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Jing Li ◽  
Marlene Dallmayer ◽  
Thomas Kirchner ◽  
Julian Musa ◽  
Thomas G.P. Grünewald
Keyword(s):  
Chromosomal Instability ◽  
Cancer Evolution

scholarly journals dN/dS dynamics quantify tumour immunogenicity and predict response to immunotherapy

2020 ◽  
Author(s):  
Luis Zapata ◽  
Giulio Caravagna ◽  
Marc J Williams ◽  
Eszter Lakatos ◽  
Khalid AbdulJabbar ◽  
...  
Keyword(s):  
Clinical Response ◽  
Patient Outcomes ◽  
Immune Evasion ◽  
Cancer Evolution ◽  
Immune Selection ◽  
Primary Tumors ◽  
Synonymous Mutations ◽  
Evolutionary Genomic ◽  
Tumor Immunogenicity ◽  
Pre Treatment

AbstractImmunoediting is a major force during cancer evolution that selects for clones with low immunogenicity (adaptation), or clones with mechanisms of immune evasion (escape). However, quantifying immunogenicity in the cancer genome and how the tumour-immune coevolutionary dynamics impact patient outcomes remain unexplored. Here we show that the ratio of nonsynonymous to synonymous mutations (dN/dS) in the immunopeptidome quantifies tumor immunogenicity and differentiates between adaptation and escape. We analysed 8,543 primary tumors from TCGA and validated immune dN/dS as a measure of selection associated with immune infiltration in immune-adapted tumours. In a cohort of 308 metastatic patients that received immunotherapy, pre-treatment lesions in non-responders showed increased immune selection (dN/dS<1), whereas responders did not and instead harboured a higher proportion of genetic escape mechanisms. Ultimately, these findings highlight the potential of evolutionary genomic measures to predict clinical response to immunotherapy.

Chromosomal instability (CIN): what it is and why it is crucial to cancer evolution

2013 ◽  
Vol 32 (3-4) ◽  
pp. 325-340 ◽  
Author(s):  
Henry H. Heng ◽  
Steven W. Bremer ◽  
Joshua B. Stevens ◽  
Steven D. Horne ◽  
Guo Liu ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Cancer Evolution

scholarly journals Karzinogenese: Big Bang oder kontinuierliche Evolution?

BIOspektrum ◽  
2020 ◽  
Vol 26 (7) ◽  
pp. 718-720
Author(s):  
Kerstin Haase ◽  
Roland F. Schwarz
Keyword(s):  
Chromosomal Instability ◽  
Classical Model ◽  
Big Bang ◽  
Cancer Evolution ◽  
Tumour Heterogeneity ◽  
Cancer Genomes ◽  
Big Bang Model ◽  
Personalised Treatment ◽  
The Big Bang ◽  
Shed Light

AbstractIntra-tumour heterogeneity is a key characteristic of tumours and poses significant clinical challenges. Despite extensive research, the evolutionary processes shaping cancer genomes are not yet fully understood. We here discuss two conflicting theories about the evolution of solid tumours: the Big Bang model and the classical model of continuous evolution. Using chromosomal instability we shed light on the preferred mode of cancer evolution and its implications for personalised treatment.

Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution

2021 ◽  
pp. candisc.0725.2020
Author(s):  
Subramanian Venkatesan ◽  
Mihaela Angelova ◽  
Clare Puttick ◽  
Haoran Zhai ◽  
Deborah R Caswell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Replication ◽  
Chromosomal Instability ◽  
Replication Stress ◽  
Cancer Evolution ◽  
Dna Replication Stress

scholarly journals Immune pressures drive the promoter hypermethylation of neoantigen genes

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Ming Yi ◽  
Bing Dong ◽  
Qian Chu ◽  
Kongming Wu
Keyword(s):  
Antigen Presentation ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Immune Escape ◽  
Promoter Hypermethylation ◽  
Cancer Evolution ◽  
Cancer Immunoediting ◽  
Immune Attack ◽  
Mechanisms Of Carcinogenesis

AbstractCancer cells with strong immunogenicity are susceptible for elimination by cancer immunoediting, while the subpopulations with weak immunogenicity survive. As a result, a subset of cancer cells evade the immune attack and evolve into overt clinical lesions. During cancer evolution, it has been well established that multiple alterations such as the dysfunction of antigen presentation machinery and the upregulation of immunosuppressive signals (e.g. PD-L1) play important roles in immune escape. Recently, promoter hypermethylation of neoantigen genes has been proposed to be a vital mechanism of immunoediting. This epigenetically mediated immune evasion enriches the mechanisms of carcinogenesis.

A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

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