Novel microdeletion in the transforming growth factor beta type II receptor gene is associated with giant and large cell variants of nonsmall cell lung carcinoma.
Genes Chromosomes Cancer
; 46(2): 192-201, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17117417
ABSTRACT
Mutations in the tumor suppressor gene transforming growth factor beta (TGFB) Type II receptor (TGFBR2) are frequently found in many cancers with microsatellite instability, but are less common in lung cancer. In the present study, we looked for mutations in TGFBR2 in nonsmall cell lung carcinoma (NSCLC) cells and tissues. A novel homozygous microdeletion (c.492_507del) was identified in two cell lines derived from the same giant cell carcinoma (GCC) and was confirmed in the corresponding tumor tissues. Furthermore, a heterozygous c.492_507del was found in the germ-line of one patient, as well as in the other GCC cases and some large cell carcinomas (LCC) but not in other subtypes of NSCLC. The 16 bp-microdeletion introduced a premature stop codon at positions 590-592 of the cDNA, resulting in a truncated TGFBR2 protein with a mutated transmembrane domain and loss of kinase domain. The GCC cells were characterized as being unresponsive to TGFB induction both in growth inhibition and stimulation of extracellular matrix protein. Moreover, after the reconstitution of wild-type TGFBR2 expression, the sensitivity to TGFB was restored. Therefore, mutated TGFBR2 seems to play an important role in the abrogation of TGFB signal transduction in GCC cells.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Serina-Treonina Quinasas
/
Receptores de Factores de Crecimiento Transformadores beta
/
Carcinoma de Células Grandes
/
Carcinoma de Células Gigantes
/
Carcinoma de Pulmón de Células no Pequeñas
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Genes Chromosomes Cancer
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2007
Tipo del documento:
Article