title: Analysis of PIK3CA exon 9 and 20 mutations in breast cancers using PCR-HRM and PCR-ARMS: correlation with clinicopathological criteria.
abstract: 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 anti‑human 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 (κ=0.845; P<0.001). PCR-ARMS             was found to be more sensitive than PCR-HRM (sensitivity 0.5 and 5-10% of mutated             DNA, respectively). We propose that PCR-HRM and PCR-ARMS can be combined for the             cost-effective routine clinical identification of PIK3CA mutations for the purpose             of personalizing therapy for invasive breast cancers.
authors: Department of Biopathology, Centre Alexis Vautrin, F-54519 Vandoeuvre-lès-Nancy Cedex, France. a.harle@nancy.unicancer.fr
authors: Alexandre
authors: A
authors: Harlé
authors: Maëva
authors: M
authors: Lion
authors: Nicolas
authors: N
authors: Lozano
authors: Marie
authors: M
authors: Husson
authors: Valentin
authors: V
authors: Harter
authors: Pascal
authors: P
authors: Genin
authors: Jean-Louis
authors: JL
authors: Merlin
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D017354:Point Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D044366:Transition Temperature
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human