title: Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients.
abstract: Carcinomas initiate and progress due to genetic and epigenetic alterations in epithelial cells. However, recently, these alterations have also been reported in stromal fibroblasts. The gain-of-function mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in many cancers with a current global incidence of 26% (18-40%) in breast carcinomas. We analyzed the mutational frequency of PIK3CA of three hotspots (exons 1, 9, and 20) in 81 primary invasive breast cancers (BC) and 25 cultured breast cancer-associated fibroblast (CAF) samples by Sanger sequencing in Arab breast cancer patients. Associations between the incidence of any PIK3CA mutation and several clinicopathologic characteristics were assessed using chi-square tests for categorical or t test for continuous variables. Furthermore, survival curves were estimated using the Kaplan-Meier method with the log rank test to evaluate the significance of their differences. We identified a total of 21 PIK3CA missense mutations with a frequency of 25.9%. The majority of the mutations, 17 out of 21 (81%), were in exon 20 (p.His1047Arg, p.His1047Lys, p.Thr1025Ala, p.Gly1049Arg, p.Asp1056Asn) while the remainder, 4 out of 21 (19%) were in exon 9 (p.Glu545Lys). PIK3CA mutations were significantly associated with lower grade and hormone receptor positivity. Although there was a favorable trend in overall survival for patients whose tumor harbored PIK3CA mutations, the difference was not statistically significant (P = 0.10). However, we did not detect any somatic mutations in CAFs. Furthermore, we have shown a high prevalence (8.2-fold) of a silent variant (SNP, rs17849079) in the Arab breast cancer population compared with disease-free individuals.
authors: Department of Molecular Oncology; King Faisal Specialist Hospital and Research Center; Riyadh, Saudi Arabia.
authors: Bedri
authors: B
authors: Karakas
authors: Dilek
authors: D
authors: Colak
authors: Namik
authors: N
authors: Kaya
authors: Hazem
authors: H
authors: Ghebeh
authors: Abeer
authors: A
authors: Al-Qasem
authors: Fawziah
authors: F
authors: Hendrayani
authors: Mohamed
authors: M
authors: Toulimat
authors: Taher
authors: T
authors: Al-Tweigeri
authors: Ben Ho
authors: BH
authors: Park
authors: Abdelilah
authors: A
authors: Aboussekhra
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016022:Case-Control Studies; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012529:Saudi Arabia / Q000453:epidemiology; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human
keywords: CAF; PI3K; PIK3CA; SNP; breast cancer; mutation
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