Analysis of PIK3CA exon 9 and 20 mutations in breast cancers using PCR-HRM and PCR-ARMS: correlation with clinicopathological criteria.
Fiche publication
Date publication
mars 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HARLE Alexandre, Pr MERLIN Jean-Louis
Tous les auteurs :
Harle A, Lion M, Lozano N, Husson M, Harter V, Genin P, Merlin JL
Lien Pubmed
Résumé
Phosphatidylinositol-3-kinases (PI3K) are essential for cell signaling, proliferation, differentiation and survival. The catalytic subunit of PI3K, encoded by the PIK3CA oncogene, is mutated in 18-45% of breast carcinomas. These mutations, involved in tumorigenic processes, activate the PI3K/AKT/mTOR signaling pathway. Resistance to antihuman epidermal growth factor receptor, hormonal or anti-PI3K therapies have been described in breast carcinomas bearing activation of the PI3K signaling pathway. The present study reports the evaluation of PIK3CA exon 9 and 20 mutations in 149 invasive breast cancer cases using a validated PCR-high resolution melting assay (PCR-HRM). An amplification refractory mutation system (PCR-ARMS) using allele-specific scorpion primers was used to detect hotspot mutations in exons 9 (c.1624G-->A and c.1633G-->A) and 20 (c.3140A-->G and c.3140A-->T) in 118 tumor specimens. No correlation was observed with age at diagnosis, histological type, hormone receptor and HER2 status. PIK3CA exon 9 and 20 mutations were found to be related to Scarff-Bloom-Richardson (SBR) grade with a lower rate of mutations and a higher frequency of exon 9 mutations in SBRI and exon 20 mutations in SBRII/III tumors. No difference was observed in the incidence rates of the two different mutations screened for each exon in any subcategory. A statistically significant correlation was found between PCR-HRM and PCR-ARMS (kappa=0.845; P
Référence
Oncol Rep. 2013 Mar;29(3):1043-52