RESUMEN
Recent reports from US and Japan have established that mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (Egfr) occur in a subset of patients with lung cancer that respond to therapy with gefitinib, a TK inhibitor. To gain further insights into the role of Egfr in carcinogenesis of lung and tumors of diverse histology, that are currently under investigation with drugs of the same class, we have taken in examination a panel of tumors consisting in 110 pulmonary adenocarcinomas, 40 pulmonary squamous carcinomas, 40 gastric adenocarcinomas and 40 colorectal adenocarcinomas. The sequence analysis of exon 19 and 21 of the Egfr has allowed the identification of 10 cases exhibiting specific deletions in exon 19 and 1 case with point mutation in a conserved residue in exon 21. All Egfr mutations occur specifically in lung adenocarcinomas while tumors of different histology result unaffected. The rate of mutation affecting these other tumors is either very rare, involves different domains of the receptor or other tyrosine kinases. The molecular analysis of the Egfr gene can help identify patients that will benefit from gefitinib therapy.
Asunto(s)
Receptores ErbB/genética , Mutación , Neoplasias/genética , Humanos , Neoplasias/patologíaRESUMEN
In spinocerebellar ataxia type 2 (SCA-2), a difference of three CAG repeats distinguishes normal alleles (14 to 31 repeats) from pathogenic alleles (34 to 57 repeats). All sequenced pathogenic alleles have a pure CAG repeat structure, whereas interrupted repeats have been seen exclusively in normal alleles. The authors present two patients with sporadic SCA with an interrupted 34-CAG repeat allele, (CAG)24(CAA)(CAG)9, who showed a phenotype compatible with SCA-2. The interrupted allele coding for a 34 pure polyglutamine tract may cause the SCA phenotype.
Asunto(s)
Proteínas/genética , Ataxias Espinocerebelosas/genética , Repeticiones de Trinucleótidos , Anciano , Alelos , Ataxinas , Atrofia , Corteza Cerebelosa/patología , Análisis Mutacional de ADN , Humanos , Imagen por Resonancia Magnética , Masculino , Proteínas del Tejido Nervioso , Penetrancia , Fenotipo , Ataxias Espinocerebelosas/patologíaRESUMEN
The use of DNA restriction fragment length polymorphisms (RFLP) to analyze variable number of tandem repeat (VNTR) sequences dispersed in the human genome, has become a powerful tool for the study of population genetics due to the very substantial polymorphism involved. Because the markers usually employed for twin zygosity determination (such as sex combination, placentation, HLA typing, blood group antigens, etc) may not be uniformly informative, we propose the use of synthetic olygonucleotides, representing VNTR "core" sequences, for the determination of zygosity in twins.
Asunto(s)
Polimorfismo de Longitud del Fragmento de Restricción , Secuencias Repetitivas de Ácidos Nucleicos , Gemelos/genética , Secuencia de Bases , Antígenos de Grupos Sanguíneos/genética , Marcadores Genéticos , Antígenos HLA/genética , Humanos , Datos de Secuencia Molecular , Sondas de Oligonucleótidos , Gemelos Dicigóticos , Gemelos MonocigóticosRESUMEN
The hybridoma technique was used to produce a mouse monoclonal antibody, designated as XI 21.4, which belongs to the IgG2a class. It is active in complement-dependent cytotoxicity and detects a B-cell antigenic determinant associated with DR1, DR4, DRw10, and, possibly, DRw9. Microfingerprinting of the immunoprecipitate from a homozygous DR4 cell line shows a typical alpha DR pattern and a beta pattern coinciding with that of DR4 molecules.