Title |
Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers
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Published in |
Nature Communications, September 2016
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DOI | 10.1038/ncomms12685 |
Pubmed ID | |
Authors |
Mandar Deepak Muzumdar, Kimberly Judith Dorans, Katherine Minjee Chung, Rebecca Robbins, Tuomas Tammela, Vasilena Gocheva, Carman Man-Chung Li, Tyler Jacks |
Abstract |
Although it has become increasingly clear that cancers display extensive cellular heterogeneity, the spatial growth dynamics of genetically distinct clones within developing solid tumours remain poorly understood. Here we leverage mosaic analysis with double markers (MADM) to trace subclonal populations retaining or lacking p53 within oncogenic Kras-initiated lung and pancreatic tumours. In both models, p53 constrains progression to advanced adenocarcinomas. Comparison of lineage-related p53 knockout and wild-type clones reveals a minor role of p53 in suppressing cell expansion in lung adenomas. In contrast, p53 loss promotes both the initiation and expansion of low-grade pancreatic intraepithelial neoplasia (PanINs), likely through differential expression of the p53 regulator p19ARF. Strikingly, lineage-related cells are often dispersed in lung adenomas and PanINs, contrasting with more contiguous growth of advanced subclones. Together, these results support cancer type-specific suppressive roles of p53 in early tumour progression and offer insights into clonal growth patterns during tumour development. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 6 | 35% |
United Kingdom | 2 | 12% |
Switzerland | 1 | 6% |
Canada | 1 | 6% |
China | 1 | 6% |
India | 1 | 6% |
Unknown | 5 | 29% |
Demographic breakdown
Type | Count | As % |
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Scientists | 10 | 59% |
Members of the public | 7 | 41% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 3% |
Korea, Republic of | 1 | <1% |
Unknown | 114 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 24 | 20% |
Student > Ph. D. Student | 22 | 18% |
Student > Bachelor | 14 | 12% |
Student > Master | 10 | 8% |
Other | 5 | 4% |
Other | 17 | 14% |
Unknown | 27 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 31 | 26% |
Agricultural and Biological Sciences | 28 | 24% |
Medicine and Dentistry | 14 | 12% |
Immunology and Microbiology | 3 | 3% |
Neuroscience | 2 | 2% |
Other | 11 | 9% |
Unknown | 30 | 25% |