title: Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes.
abstract: Understanding how cancer genes are mutated in individual tumors is an important issue with potential clinical and therapeutic impact. This is especially relevant with recently developed targeted therapies since mutated genes can be targets and/or predictors. However, to date, gene mutation profiling in individual tumors is still underexplored. Breast cancer is composed of various subtypes. We presumed that this heterogeneity reflected the involvement of different molecular mechanisms including gene mutations that affect defined signaling pathways. Unlike the majority of published mutational studies, this study was aimed to draw a mutation profile in individual tumors by screening a panel of cancer genes in the same tumor. Thus, five genes frequently mutated in breast cancers: TP53, PIK3CA, PTEN, CDH1, and AKT1 were screened in each of 120 human primary breast tumors. Mutations in at least one of these genes were found in 62.5% of the tumors, of which the majority carried a single-gene mutation. Interestingly, a substantial proportion of tumors carried mutations either in TP53 or in genes of the PI3K pathway (PIK3CA or PTEN or AKT1). These two distinct mutation patterns were significantly associated to hormone receptor expression but independent of HER2 status.
authors.affiliation: Laboratoire de Recherche Translationnelle, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cedex 08, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boyault
authors.forename: Youenn
authors.initials: Y
authors.lastname: Drouet
authors.forename: Claudine
authors.initials: C
authors.lastname: Navarro
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Eric
authors.initials: E
authors.lastname: Tabone
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D015820:Cadherins / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D011987:Receptors, Steroid; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human