title: Mutation of genes of the PI3K/AKT pathway in breast cancer supports their potential importance as biomarker for breast cancer aggressiveness.
abstract: Deregulation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is closely associated with cancer development and cancer progression. PIK3CA, AKT1, and PTEN are the fundamental molecules of the PI3K/AKT pathway with increased mutation rates in cancer cases leading to aberrant regulation of the pathway. Even though molecular alterations of the PI3K/AKT pathway have been studied in breast cancer, correlations between specific molecular alterations and clinicopathological features remain contradictory. In this study, we examined mutations of the PI3K/AKT pathway in 75 breast carcinomas using high-resolution melting analysis and pyrosequencing, in parallel with analysis of relative expression of PIK3CA and AKT2 genes. Mutations of PIK3CA were found in our cohort in 21 cases (28 %), 10 (13 %) in exon 9 and 11(15 %) in exon 20. Mutation frequency of AKT1 and PTEN genes was 4 and 3 %, respectively. Overall, alterations in the PI3K/AKT signaling cascade were detected in 35 % of the cases. Furthermore, comparison of 50 breast carcinomas with adjacent normal tissues showed elevated PIK3CA messenger RNA (mRNA) levels in 18 % of tumor cases and elevated AKT2 mRNA levels in 14 %. Our findings, along with those of previous studies, underline the importance of the PI3K/AKT pathway components as potential biomarkers for breast carcinogenesis.
authors.affiliation: First Department of Pathology, "Laikon" General Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Assias 75, Goudi, 11527, Athens, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Tserga
authors.affiliation: First Department of Pathology, "Laikon" General Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Assias 75, Goudi, 11527, Athens, Greece.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Chatziandreou
authors.affiliation: First Propaedeutic Department of Surgery, Hippocration University Hospital, University of Athens, Athens, Greece.
authors.forename: Nicolaos V
authors.initials: NV
authors.lastname: Michalopoulos
authors.affiliation: First Department of Pathology, "Laikon" General Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Assias 75, Goudi, 11527, Athens, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: First Department of Pathology, "Laikon" General Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Assias 75, Goudi, 11527, Athens, Greece. asaetta@med.uoa.gr.
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: AKT; Breast cancer; HRM; PI3K/AKT; PIK3CA; Pyrosequencing