title: Spectrum of somatic EGFR, KRAS, BRAF, PTEN mutations and TTF-1 expression in Brazilian lung cancer patients.
abstract: Lung cancer is the leading global cause of cancer-related mortality. Inter-individual variability in treatment response and prognosis has been associated with genetic polymorphisms in specific genes: EGFR, KRAS, BRAF, PTEN and TTF-1. Somatic mutations in EGFR and KRAS genes are reported at rates of 15-40% in non-small cell lung cancer (NSCLC) in ethnically diverse populations. BRAF and PTEN are commonly mutated genes in various cancer types, including NSCLC, with PTEN mutations exerting an effect on the therapeutic response of EGFR/AKT/PI3K pathway inhibitors. TTF-1 is expressed in approximately 80% of lung adenocarcinomas and its positivity correlates with higher prevalence of EGFR mutation in this cancer type. To determine molecular markers for lung cancer in Brazilian patients, the rate of the predominant EGFR, KRAS, BRAF and PTEN mutations, as well as TTF-1 expression, was assessed in 88 Brazilian NSCLC patients. EGFR exon 19 deletions (del746-750) were detected in 3/88 (3·4%) patients. Activating KRAS mutations in codons 12 and 61 were noted in five (5·7%) and two (2·3%) patients, respectively. None of the common somatic mutations were detected in either the BRAF or PTEN genes. TTF-1 was overexpressed in 40·7% of squamous-cell carcinoma (SCC). Our findings add to a growing body of data that highlights the genetic heterogeneity of the abnormal EGFR pathway in lung cancer among ethnically diverse populations.
authors.affiliation: Faculdade de Ciências Médicas, Centro de Ensino Superior e Desenvolvimento, Campina Grande, 58411-020, Brasil.
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Carneiro
authors.affiliation: Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brasil.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Couto
authors.affiliation: Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brasil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Bastos-Rodrigues
authors.affiliation: Department of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brasil.
authors.forename: Maria Aparecida C
authors.initials: MA
authors.lastname: Bicalho
authors.affiliation: Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brasil.
authors.forename: Paula V
authors.initials: PV
authors.lastname: Vidigal
authors.affiliation: Hospital Julia Kubitscheck, Belo Horizonte, 30620-470, Brasil.
authors.forename: Alyne
authors.initials: A
authors.lastname: Vilhena
authors.affiliation: Hospital Julia Kubitscheck, Belo Horizonte, 30620-470, Brasil.
authors.forename: Nilson F
authors.initials: NF
authors.lastname: Amaral
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: Allen E
authors.initials: AE
authors.lastname: Bale
authors.affiliation: The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.affiliation: Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brasil.
authors.forename: Luiz
authors.initials: L
authors.lastname: De Marco
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D014157:Transcription Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins