title: PIK3CA amplification is predictive of poor prognosis in Tunisian patients with nasopharyngeal carcinoma.
abstract: PI3Ks (phosphatidylinositol 3-kinases) are lipid kinases that regulate signalling pathways involved in cell proliferation, motility, and adhesion. Somatic mutations and amplification of the PIK3CA gene have been reported in various types of human cancers. However, little is known about the frequency and prognosis role of PIK3CA activation in nasopharyngeal carcinoma (NPC). This study was conducted with the aim to screen for PIK3CA mutations in the two hot spot regions (exons 9 and 20) and to investigate for the PIK3CA gene amplification combined with the expression analysis of the phosphorylated Akt (pAkt). We showed that among 88 specimens, none had mutation in the helical domain (exon 9) and only one (1.13%) had mutation in the kinase domain (exon 20). On the other hand, PIK3CA gene amplification was found in 21.6% of cases and was strongly associated with distant metastasis (P = 0.002), lymph node involvement (P = 0.032), and advanced tumor stage (P < 0.001). Moreover, patients with PIK3CA copy number gain have a significant reduced overall survival time (P log rank = 0.02). We concluded that PIK3CA gene amplification is frequent in NPC and occurs in the advanced stage of NPC. Moreover, our finding emphasizes the association of PIK3CA gene amplification with worse prognosis in nasopharyngeal carcinoma.
authors.affiliation: Laboratory of Cancer Genetic and Production of Recombinant Proteins, Route Sidi, Mansour Sfax, Sfax, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Fendri
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.forename: Wafa
authors.initials: W
authors.lastname: Mnejja
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.forename: Jamel
authors.initials: J
authors.lastname: Daoud
authors.forename: Mounir
authors.initials: M
authors.lastname: Frikha
authors.forename: Abdelmonem
authors.initials: A
authors.lastname: Ghorbel
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D058534:Class I Phosphatidylinositol 3-Kinases; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000401:mortality; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human