Epidemiology of Doublet/Multiplet Mutations in Lung Cancers: Evidence that a Subset Arises by Chronocoordinate Events
2008

Epidemiology of Doublet Mutations in Lung Cancers

Sample size: 1627 publication Evidence: moderate

Author Information

Author(s): Chen Zhenbin, Feng Jinong, Buzin Carolyn H., Sommer Steve S.

Primary Institution: City of Hope National Medical Center

Hypothesis

What is the epidemiology of doublet mutations in the EGFR and TP53 genes in lung cancer?

Conclusion

Doublet mutations in the EGFR and TP53 genes are more frequent in human lung cancer than in normal mouse tissue, suggesting a significant role of chronocoordinate events in their occurrence.

Supporting Evidence

  • Doublets in the EGFR gene are elevated about eight-fold compared to spontaneous doublets in mouse.
  • About 32% of doublets in the EGFR gene are very closely spaced (≤30 nt).
  • Doublets in the TP53 gene are also closely spaced in 33% of cases.

Takeaway

This study found that lung cancer has more double mutations than normal tissues, which might happen in a specific order during cell division.

Methodology

EGFR mutations were collected from 66 published papers and an updated mutation database, while TP53 mutations were sourced from the IARC database.

Potential Biases

Potential bias due to the exclusion of certain mutation types and the reliance on published data.

Limitations

The study did not analyze allelic data for heterozygous TP53 doublets.

Participant Demographics

The average age of patients with doublets was 65.8 years, with no significant differences in race, ethnicity, gender, or smoking status observed.

Statistical Information

P-Value

0.03

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0003714

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