Somatic mutations in cancer prognosis and prediction: lessons from TP53 and EGFR genes.
OBJECTIVE
We used two examples of genes, TP53 and EGFR, which are somatically altered by intragenic mutations in common cancer types to illustrate how somatic mutations have followed very different routes to clinical applications.


RESULTS
TP53 somatic mutations are frequent in many cancers. Their prognostic and predictive values are currently assessed in several clinical trials and TP53 gene therapy is in use in China. Mutations in EGFR have been proved to be predictive of response to tyrosine kinase inhibitors, allowing for the licensing of gefitinib in lung adenocarcinomas carrying a mutated EGFR gene.


CONCLUSIONS
With the accumulation of knowledge on the predictive and prognostic value of somatic mutations, and with recent advances in large-scale sequencing techniques and reduction in cost of sequencing, sequencing several genes in human tumors is on the verge of becoming routine clinical practice.
International Agency for Research on Cancer, Group of Molecular Carcinogenesis, Lyon, France. molivier@iarc.fr
Magali
M
Olivier
Philippe
P
Taniere
D018773:Genes, erbB-1; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis