Comprehensive characterization of the commonalities and differences of numerical and structural chromosomal instability in human cancers
Actions 
Order Studies
Many cancer cells are chromosomally unstable, a phenotype describing a tendency for accumulating chromosomal aberrations. Entire chromosomes tend to be gained or lost, which is called whole chromosome instability (W-CIN). Structural chromosomal instability (S-CIN) describes an increased rate of gaining, losing or translocating smaller parts of chromosomes. Here we analyse data from 33 cancer types to find differences and commonalities between W-CIN and S-CIN. We find, that W-CIN is strongly linked to whole genome doubling (WGD), whereas S-CIN is associated with a specific DNA damage repair pathway. Both W-CIN and S-CIN are difficult to target using currently available compounds and have distinct prognostic values. The activity of the drug resistance gene \textit{CKS1B} is associated with both CIN types, which merits further investigation as potential CIN target. In addition, we identify a potential copy number based mechanism promoting signalling of the important \textit{PI3K} cancer pathway in high CIN tumours.
Investigation position:
Export PNG
Download
Creators and SubmitterViews: 391
Created: 17th Jan 2022 at 12:30
TagsThis item has not yet been tagged.
Related items
Projects: Test, SP-3: A statistical modeling approach to identify common triggers for replication stress and mitotic chromosome missegregation, SP-1: Deciphering signaling pathways that promote accurate chromosome segregation after replication stress, SP-2: Molecular mechanisms of replication stress-induced mitotic chromosome missegregation, SP-4: Centrosome integrity as a determinant of replication stress and mitotic dysfunction, SP-5: Impaired chromosome integrity caused by mutations in members of the BTR complex, SP-8: The causes of replication stress in response to whole chromosomal aneuploidy, SP-Z: NGS-based approaches for systematic analysis of genomic and chromosome instability Bernd Wollnik, Göttingen, SP9: Mutual impact of replication origin firing regulation and mitotic chromosome segregation
Institutions: University of Applied Sciences Koblenz
Xiaoxiao Zhang is a Biomathematics and Bioinformatics PhD student in Maik Kschischo's group at the University of Applied Sciences Koblenz. She works in the FOR2800 research unit.
Our Research Unit addresses an important question on the origin of chromosome instability (CIN), which causes structural as well as numerical chromosome aberrations. Importantly, CIN and increased levels of chromosome aberrations are closely associated with many human diseases including cancer, neurodegenerative diseases and age-related syndromes and can act as key drivers for disease development and progression. An important condition that causes structural chromosome instability (S-CIN) leading ...
Projects: SP-3: A statistical modeling approach to identify common triggers for replication stress and mitotic chromosome missegregation, SP-1: Deciphering signaling pathways that promote accurate chromosome segregation after replication stress, SP-2: Molecular mechanisms of replication stress-induced mitotic chromosome missegregation, SP-4: Centrosome integrity as a determinant of replication stress and mitotic dysfunction, SP-5: Impaired chromosome integrity caused by mutations in members of the BTR complex, SP-6: Proteomics of mitotic inter sister chromatid junctions, SP-8: The causes of replication stress in response to whole chromosomal aneuploidy, SP-Z: NGS-based approaches for systematic analysis of genomic and chromosome instability Bernd Wollnik, Göttingen, SP9: Mutual impact of replication origin firing regulation and mitotic chromosome segregation
Web page: https://for2800.de/
Replication stress (RS) and chromosomal instability (CIN) are commonly observed features of cancer cells. RS has a destabilizing effect on the genome and, vice versa, whole chromosome aneuploidy as a result of CIN can induce a RS response. Our preliminary data analysis of cancer genomic data suggests a tendency of whole chromosome CIN (W-CIN) to co-occur with structural CIN (S-CIN), whilst S-CIN can also appear in numerical stable tumors. We also found a significant positive correlation of mRNA ...
We implemented the pan-cancer chromosomal instability association studies pipeline using R-3.6. The source code and data are available at https://github.com/mcmzxx/pancan_cin
Submitter: Xiaoxiao Zhang
Investigation: Comprehensive characterization of the commonali...
Assays: No Assays
Abstract (Expand)
Editor:
Date Published: No date defined
Publication Type: Journal
