Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma - rationale for comprehensive mutation profiling
A partir de données portant sur 1 125 patients atteints d'un adénocarcinome pulmonaire, cette étude identifie la fréquence de divers gènes mutés en association avec la présence d'une mutation du gène PIK3CA
PIK3CA encodes the p110α subunit of the mitogenic signaling protein phosphatidylinositol 3-kinase (PI3K). PIK3CA mutations in the helical binding domain and the catalytic subunit of the protein have been associated with tumorigenesis and treatment resistance in various malignancies. Characteristics of patients with PIK3CA-mutant lung adenocarcinomas have not been reported. We examined EGFR, KRAS, BRAF, HER2, PIK3CA, AKT1, NRAS, MEK1, and ALK in patients with adenocarcinoma of the lung to identify driver mutations. Clinical data were obtained from the medical records of individuals with mutations in PIK3CA. Twenty-three of 1125 (2%, 95% confidence interval (CI) 1-3%) patients had a mutation in PIK3CA, 12 in Exon 9 (10 E545K, 2 E542K) and 11 in Exon 20 (3 H1047L, 8 H1047R). The patients (57% women) had a median age of 66 at diagnosis (range 34-78). Eight patients (35%) were never smokers. Sixteen of 23 (70%, 95% CI 49 - 86%) had coexisting mutations in other oncogenes - 10 KRAS, 1 MEK1, 1 BRAF, 1 ALK rearrangement, and 3 EGFR exon 19 deletions. We conclude that PIK3CA mutations occur in lung adenocarcinomas, usually concurrently with EGFR, KRAS, and ALK. The impact of PIK3CA mutations on the efficacy of targeted therapies such as erlotinib and crizotinib is unknown. Given the high frequency of overlapping mutations, comprehensive genotyping should be performed on tumor specimens from patients enrolling on clinical trials of PI3K and other targeted therapies.
http://mct.aacrjournals.org/content/early/2011/11/29/1535-7163.MCT-11-0692.abstract