Publication:
Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer.

Thumbnail Image

Date

2010-04-13

Authors

Sánchez-Muñoz, Alfonso
Gallego Domínguez, Elena María
Luque, Vanessa de
Pérez-Rivas, Luís G
Vicioso Recio, Luís
Ribelles Entrena, Nuria
Lozano Castro, José
Alba Conejo, Emilio

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

BioMed Central
Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

BACKGROUND Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies. METHODS Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp. RESULTS We found no evidence of KRAS oncogenic mutations in all analyzed tumors. CONCLUSIONS This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.

Description

Journal Article; Research Support, Non-U.S. Gov't;

MeSH Terms

Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::DNA Mutational Analysis
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::Immunohistochemistry
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Keratins::Keratins, Type II::Keratin-5
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Keratins::Keratins, Type II::Keratin-6
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Neoplasms, Basal Cell
Medical Subject Headings::Health Care::Health Services Administration::Patient Care Management::Patient Selection
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, Epidermal Growth Factor
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, Biological
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases::GTP-Binding Proteins::Monomeric GTP-Binding Proteins::ras Proteins
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms

DeCS Terms

CIE Terms

Keywords

KRT5 protein, human, EGFR protein, human, ERBB2 protein, human, KRAS protein, human, Análisis Mutacional de ADN, Regulación Neoplásica de la Expresión Génica, Inmunohistoquímica, Queratina-5, Queratina-6, Mutación, Neoplasias vasocelulares, Selección de pacientes, Reacción en Cadena de la Polimerasa, Inhibidores de las Proteína Quinasas, Proteínas Proto-Oncogénicas, Receptor del Factor de Crecimiento Epidérmico, Receptores estrogénicos, Receptores de progesterona, Marcadores biológicos de tumor, Marcadores tumorales, Proteínas ras, Neoplasias de la mama

Citation

Sánchez-Muñoz A, Gallego E, Luque V de, Pérez-Rivas LG, Vicioso L, Ribelles N, et al. Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer. BMC Cancer; 10:136