Journal
NATURE
Volume 531, Issue 7595, Pages 471-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature17157
Keywords
-
Categories
Funding
- National Cancer Institute
- Center grant for Cancer Target Discovery and Development
- Memorial Sloan Kettering Cancer Center Support Grant
- American Association for Cancer Research Millennium Fellowship in Lymphoma Research
- Thousand Young Talents Plan
- National Natural Science Foundation of China [81522003, 81570150]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available