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1.
Virchows Arch ; 472(5): 717-725, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29333594

RESUMO

Wild-type status of KRAS and the NRAS gene (exon 2, 3, and 4) in the tumor should be determined before treatment of metastatic colorectal cancer (mCRC) patients with EGFR-targeting agents. There is a large variation in test methods to determine RAS status, and more sensitive detection methods were recently introduced. Data from quality assessment programs indicate substantial error rates. This study assessed the completeness and correctness of RAS testing in European laboratories that successfully passed external quality assessment (EQA). Participants were requested to send material of their most recent ten patients with mCRC who had been tested for RAS status. Isolated DNA, a hematoxylin and eosin stained tissue slide with a marked area for macrodissection and accompanying patient reports were requested. Samples were reevaluated in a reference laboratory by using a next-generation sequencing approach. In total, 31 laboratories sent in the requested material (n = 309). Despite regulations for anti-EGFR therapy, one institute did not perform full RAS testing. Reanalysis was possible for 274 samples with sufficient DNA available. In the hotspot codons of KRAS and NRAS, seven discordant results were obtained in total, five of them leading to a different prediction of anti-EGFR therapy efficacy (2%; n = 274). Results show that oncologists can rely on the quality of laboratories with good performance in EQA. Oncologists need to be aware that the testing laboratory participates successfully in EQA programs. Some EQA providers list the good performing laboratories on their website.


Assuntos
Neoplasias Colorretais/genética , GTP Fosfo-Hidrolases/análise , Oncologia/normas , Proteínas de Membrana/análise , Proteínas Proto-Oncogênicas p21(ras)/análise , Garantia da Qualidade dos Cuidados de Saúde , GTP Fosfo-Hidrolases/genética , Testes Genéticos/normas , Humanos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas p21(ras)/genética
2.
J Cyst Fibros ; 7(3): 179-96, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18456578

RESUMO

It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Análise Mutacional de DNA , Humanos , Estado Nutricional/genética , Polimorfismo Genético , Prognóstico , Processamento de Proteína , Controle de Qualidade , Testes de Função Respiratória , Terminologia como Assunto
3.
Eur J Hum Genet ; 8 Suppl 2: S2-24, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11108532

RESUMO

These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external quality assurance, and for reporting the results, including the requirements of minimal services in mutation testing, the nomenclature for describing mutations, procedures to control false-positive amplification reactions and to validate tests, and guidelines to implement a quality system in a molecular diagnostic laboratory are reviewed.


Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/genética , Testes Genéticos/métodos , Acreditação , Adolescente , Adulto , Criança , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Bases de Dados como Assunto , Europa (Continente) , Reações Falso-Positivas , Frequência do Gene , Aconselhamento Genético/métodos , Predisposição Genética para Doença , Humanos , Infertilidade/genética , Mutação/genética , Polimorfismo Genético , Diagnóstico Pré-Natal/métodos , Controle de Qualidade , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Manejo de Espécimes , Suor , Terminologia como Assunto
4.
Nat Genet ; 25(3): 259-60, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10888869

RESUMO

To evaluate the quality of genetic testing for cystic fibrosis, 136, 145 and 159 laboratories participated in a European study in 1996, 1997 and 1998, respectively. We sent six purified DNA samples carrying the more common CFTR mutations with the request to test them using routine protocols. A panel of experts reviewed the results together with the raw data.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , DNA/análise , Erros de Diagnóstico , Testes Diagnósticos de Rotina/estatística & dados numéricos , Testes Diagnósticos de Rotina/tendências , Testes Genéticos/tendências , Humanos , Laboratórios , Mutação , Controle de Qualidade
5.
Eur J Hum Genet ; 6(2): 165-75, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9781062

RESUMO

Within the framework of the European Concerted Action on Cystic Fibrosis (Biomed-2, BMH4-CT96-0462) a quality assessment was set up for 135 European and one Australian laboratory. Six DNA samples were sent to the various laboratories. These samples carried the following CFTR genotypes: dF508/N1303K; dI507/wild; dF508/G551D; dF508/621 + 1 GtoT; R553X/wild and 1717-1 GtoA/wild. Each laboratory was asked to process the samples as they routinely do, whether they checked for all mutations or not. More than 75% of the laboratories screened for at least six of these mutations. Heteroduplex analysis was the most frequently used primary testing method (47%), in many instances followed by restriction enzyme digestion. Only a minority of the laboratories made use of a commercial CFTR mutation detection kit. On average, 91% of the laboratories correctly typed both alleles of a given DNA sample. However, 35% of the laboratories incorrectly typed one or more alleles from a total of 12 alleles included in the trial. One laboratory even failed to identify four of the different alleles correctly. The genotyping error frequency tended to be lower in laboratories which perform more than 200 CFTR mutation analyses per year. The results of this quality control trial suggest that there are many laboratories (35%) which have a percentage of errors unacceptable in a routine testing setting. The development of a consensus testing strategy for routine diagnostic laboratories and centralised mutation analysis facilities for rare or country-specific mutations in a limited number of expert centres, in combination with regular training sessions and quality assessments, should further improve genotyping.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Análise Mutacional de DNA/normas , Testes Genéticos/normas , Laboratórios/normas , Mutação , Austrália , Europa (Continente) , Genótipo , Humanos , Controle de Qualidade
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