Genome Wide Identification of Recessive Cancer Genes by Combinatorial Mutation Analysis
2008

Identifying Recessive Cancer Genes

Sample size: 700 publication Evidence: high

Author Information

Author(s): Stefano Volinia, Nicoletta Mascellani, Jlenia Marchesini, Angelo Veronese, Elizabeth Ormondroyd, Hansjuerg Alder, Jeff Palatini, Massimo Negrini, Carlo M. Croce

Primary Institution: Università degli Studi, Ferrara, Italy; Ohio State University, Columbus, Ohio, United States of America; Institute of Cancer Research, Surrey, United Kingdom

Hypothesis

We devised a novel procedure to identify human cancer genes acting in a recessive manner.

Conclusion

The study identified 154 candidate recessive cancer genes, including well-known genes like TP53, PTEN, and CDKN2A, which are frequently mutated in cancer.

Supporting Evidence

  • 154 candidate recessive cancer genes were identified with a p-value less than 1.5×10−7.
  • TP53, PTEN, and CDKN2A ranked in the top 0.5% of the studied genes.
  • The functions affected by cancer mutations overlap with known cancer genes, except for tyrosine kinases.

Takeaway

The researchers found new genes that can cause cancer when both copies are mutated, which is different from the more common cancer genes that only need one copy to be mutated.

Methodology

The study combined data from over 20,000 genes and 700 array comparative genomic hybridizations to identify recessive cancer genes based on various types of genetic alterations.

Potential Biases

Potential bias due to sequencing errors and the absence of germ-line sequences corresponding to tumor libraries.

Limitations

The study's reliance on EST data may introduce sequencing errors, and the somatic nature of detected mutations cannot be formally established.

Statistical Information

P-Value

p<1.5×10−7

Statistical Significance

p<1.5×10−7

Digital Object Identifier (DOI)

10.1371/journal.pone.0003380

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication