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

Authors: Liu, Y.; Chen, C.; Xu, Z.; Scuoppo, C.; Rillahan, C. D.; Gao, J.; Spitzer, B.; Bosbach, B.; Kastenhuber, E. R.; Baslan, T.; Ackermann, S.; Cheng, L.; Wang, Q.; Niu, T.; Schultz, N.; Levine, R. L.; Mills, A. A.; Lowe, S. W.
Article Title: Deletions linked to TP53 loss drive cancer through p53-independent mechanisms
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. © 2016 Macmillan Publishers Limited. All rights reserved.
Journal Title: Nature
Volume: 531
Issue: 7595
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2016-03-24
Start Page: 471
End Page: 475
Language: English
DOI: 10.1038/nature17157
PROVIDER: scopus
PMCID: PMC4836395
PUBMED: 26982726
Notes: Article -- Export Date: 2 May 2016 -- Source: Scopus
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MSK Authors
  1. Ross Levine
    469 Levine
  2. Scott W Lowe
    145 Lowe
  3. Jianjiong Gao
    62 Gao
  4. Barbara Spitzer
    26 Spitzer
  5. Nikolaus D Schultz
    196 Schultz
  6. Chong Chen
    11 Chen
  7. Timour Baslan
    15 Baslan
  8. Qingguo   Wang
    5 Wang