Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Yu Liu, Chong Chen, Zhengmin Xu, Claudio Scuoppo, Cory D. Rillahan, Jianjiong Gao, Barbara Spitzer, Benedikt Bosbach, Edward R. Kastenhuber, Timour Baslan, Sarah Ackermann, Lihua Cheng, Qingguo Wang, Ting Niu, Nikolaus Schultz, Ross L. Levine, Alea A. Mills and Scott W. Lowe ()
Additional contact information
Yu Liu: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center
Chong Chen: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center
Zhengmin Xu: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center
Claudio Scuoppo: Institute for Cancer Genetics, Columbia University Medical Center
Cory D. Rillahan: Memorial Sloan Kettering Cancer Center
Jianjiong Gao: Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Barbara Spitzer: Memorial Sloan Kettering Cancer Center
Benedikt Bosbach: Memorial Sloan Kettering Cancer Center
Edward R. Kastenhuber: Memorial Sloan Kettering Cancer Center
Timour Baslan: Memorial Sloan Kettering Cancer Center
Sarah Ackermann: Memorial Sloan Kettering Cancer Center
Lihua Cheng: West China Hospital, Sichuan University
Qingguo Wang: Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Ting Niu: West China Hospital, Sichuan University
Nikolaus Schultz: Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Ross L. Levine: Human Oncology & Pathogenesis Program and Leukemia Service, Memorial Sloan Kettering Cancer Center
Alea A. Mills: Cold Spring Harbor Laboratory
Scott W. Lowe: Memorial Sloan Kettering Cancer Center

Nature, 2016, vol. 531, issue 7595, 471-475

Abstract: Abstract Mutations disabling the TP53 tumour suppressor gene represent the most frequent events in human cancer and typically occur through a two-hit mechanism involving a missense mutation in one allele and a ‘loss of heterozygosity’ deletion encompassing the other. While TP53 missense mutations can also contribute gain-of-function activities that impact tumour progression, it remains unclear whether the deletion event, which frequently includes many genes, impacts tumorigenesis beyond TP53 loss alone. Here we show that somatic heterozygous deletion of mouse chromosome 11B3, a 4-megabase region syntenic to human 17p13.1, produces a greater effect on lymphoma and leukaemia development than Trp53 deletion. Mechanistically, the effect of 11B3 loss on tumorigenesis involves co-deleted genes such as Eif5a and Alox15b (also known as Alox8), the suppression of which cooperates with Trp53 loss to produce more aggressive disease. Our results imply that the selective advantage produced by human chromosome 17p deletion reflects the combined impact of TP53 loss and the reduced dosage of linked tumour suppressor genes.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature17157 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:531:y:2016:i:7595:d:10.1038_nature17157

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature17157

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().