Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types
A large proportion of tumours is characterised by numerical or structural chromosomal instability (CIN), defined as an increased rate of gaining or losing whole chromosomes (W-CIN) or of accumulating structural aberrations (S-CIN). Both W-CIN and S-CIN are associated with tumourigenesis, cancer prog...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/6/1424 |
| _version_ | 1797446954796449792 |
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| author | Xiaoxiao Zhang Maik Kschischo |
| author_facet | Xiaoxiao Zhang Maik Kschischo |
| author_sort | Xiaoxiao Zhang |
| collection | DOAJ |
| description | A large proportion of tumours is characterised by numerical or structural chromosomal instability (CIN), defined as an increased rate of gaining or losing whole chromosomes (W-CIN) or of accumulating structural aberrations (S-CIN). Both W-CIN and S-CIN are associated with tumourigenesis, cancer progression, treatment resistance and clinical outcome. Although W-CIN and S-CIN can co-occur, they are initiated by different molecular events. By analysing tumour genomic data from 33 cancer types, we show that the majority of tumours with high levels of W-CIN underwent whole genome doubling, whereas S-CIN levels are strongly associated with homologous recombination deficiency. Both CIN phenotypes are prognostic in several cancer types. Most drugs are less efficient in high-CIN cell lines, but we also report compounds and drugs which should be investigated as targets for W-CIN or S-CIN. By analysing associations between CIN and bio-molecular entities with pathway and gene expression levels, we complement gene signatures of CIN and report that the drug resistance gene <i>CKS1B</i> is strongly associated with S-CIN. Finally, we propose a potential copy number-dependent mechanism to activate the <i>PI3K</i> pathway in high-S-CIN tumours. |
| first_indexed | 2024-03-09T13:48:00Z |
| format | Article |
| id | doaj.art-4097b45972834d6da77e9ab438613fdb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:48:00Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4097b45972834d6da77e9ab438613fdb2023-11-30T20:55:19ZengMDPI AGCancers2072-66942022-03-01146142410.3390/cancers14061424Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer TypesXiaoxiao Zhang0Maik Kschischo1Department of Mathematics and Technology, University of Applied Sciences Koblenz, 53424 Remagen, GermanyDepartment of Mathematics and Technology, University of Applied Sciences Koblenz, 53424 Remagen, GermanyA large proportion of tumours is characterised by numerical or structural chromosomal instability (CIN), defined as an increased rate of gaining or losing whole chromosomes (W-CIN) or of accumulating structural aberrations (S-CIN). Both W-CIN and S-CIN are associated with tumourigenesis, cancer progression, treatment resistance and clinical outcome. Although W-CIN and S-CIN can co-occur, they are initiated by different molecular events. By analysing tumour genomic data from 33 cancer types, we show that the majority of tumours with high levels of W-CIN underwent whole genome doubling, whereas S-CIN levels are strongly associated with homologous recombination deficiency. Both CIN phenotypes are prognostic in several cancer types. Most drugs are less efficient in high-CIN cell lines, but we also report compounds and drugs which should be investigated as targets for W-CIN or S-CIN. By analysing associations between CIN and bio-molecular entities with pathway and gene expression levels, we complement gene signatures of CIN and report that the drug resistance gene <i>CKS1B</i> is strongly associated with S-CIN. Finally, we propose a potential copy number-dependent mechanism to activate the <i>PI3K</i> pathway in high-S-CIN tumours.https://www.mdpi.com/2072-6694/14/6/1424whole chromosomal instabilitystructural chromosomal instabilitywhole genome doublingintegrative analysis<i>PI3K</i> oncogenic activation |
| spellingShingle | Xiaoxiao Zhang Maik Kschischo Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types Cancers whole chromosomal instability structural chromosomal instability whole genome doubling integrative analysis <i>PI3K</i> oncogenic activation |
| title | Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types |
| title_full | Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types |
| title_fullStr | Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types |
| title_full_unstemmed | Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types |
| title_short | Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types |
| title_sort | distinct and common features of numerical and structural chromosomal instability across different cancer types |
| topic | whole chromosomal instability structural chromosomal instability whole genome doubling integrative analysis <i>PI3K</i> oncogenic activation |
| url | https://www.mdpi.com/2072-6694/14/6/1424 |
| work_keys_str_mv | AT xiaoxiaozhang distinctandcommonfeaturesofnumericalandstructuralchromosomalinstabilityacrossdifferentcancertypes AT maikkschischo distinctandcommonfeaturesofnumericalandstructuralchromosomalinstabilityacrossdifferentcancertypes |