Predisposition to Cancer Caused by Genetic and Functional Defects of Mammalian Atad5
2011

Cancer Predisposition by Atad5 Mutation

Sample size: 42 publication 10 minutes Evidence: high

Author Information

Author(s): Bell Daphne W., Sikdar Nilabja, Lee Kyoo-young, Price Jessica C., Chatterjee Raghunath, Park Hee-Dong, Fox Jennifer, Ishiai Masamichi, Rudd Meghan L., Pollock Lana M., Fogoros Sarah K., Mohamed Hassan, Hanigan Christin L., Zhang Suiyuan, Cruz Pedro, Renaud Gabriel, Hansen Nancy F., Cherukuri Praveen F., Borate Bhavesh, McManus Kirk J., Stoepel Jan, Sipahimalani Payal, Godwin Andrew K., Sgroi Dennis C., Merino Maria J., Elliot Gene, Elkahloun Abdel, Vinson Charles, Takata Minoru, Mullikin James C., Wolfsberg Tyra G., Hieter Philip, Lim Dae-Sik, Myung Kyungjae

Primary Institution: National Human Genome Research Institute, National Institutes of Health

Hypothesis

Reduced expression of mouse Atad5 would lead to genomic instability in vivo.

Conclusion

Loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis.

Supporting Evidence

  • 90% of haploinsufficient Atad5+/m mice developed tumors.
  • Atad5+/m mice displayed high levels of genomic instability.
  • Somatic mutations of ATAD5 were identified in 4.6% of sporadic human endometrial tumors.

Takeaway

Mice with a mutation in the Atad5 gene are more likely to develop tumors because their cells can't fix DNA damage properly.

Methodology

The study involved generating heterozygous Atad5+/m mice and analyzing their genomic stability and tumor development.

Participant Demographics

The study involved 42 mice, including 22 Atad5+/m mice and 20 wild type controls.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1371/journal.pgen.1002245

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