Mechanism of Retinoblastoma Gene Inactivation in the Spectrum of Neuroendocrine Lung Tumors
作者： Valérie Gouyer , Sylvie Gazzéri , Isabelle Bolon , Christiane Drevet , Christian Brambilla
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摘要: The retinoblastoma (RB) gene plays a key role in cell cycle control by regulation of G1 growth arrest. This is inactivated some human cancers and most small-cell lung carcinoma (SCLC) lines. aim this study was to analyze the mechanisms RB silencing freshly excised neuroendocrine (NE) tumors embracing entire spectrum NE neoplasms (typical atypical carcinoids, large-cell carcinomas [LCNECs], SCLCs). To mechanism inactivation tumor differentiation malignant potential, status Rb protein analyzed 37 tumors, using immunohistochemistry with five antibodies. Loss or altered expression more frequently observed high-grade (23 28, 82%) than typical carcinoids (1 9, 11%) (P < 0.001). Of 24 abnormal staining, Southern blotting showed 1 have undergone rearrangement, SSCP (single-strand conformation polymorphism) sequencing that 6 (25%) exhibited mutations exons 13-18 20-24 gene, RT-PCR (reverse transcriptase-polymerase chain reaction) revealed 14 (58%) low level entirely absent mRNA (messenger RNA) expression, whereas hypermethylation CpG-rich island at 5' end not observed. Abnormal always associated one these three alternative SCLCs analyzed, but only 50% LCNECs. These results indicate highly frequent through distinct including point expression. Different modes seem be implicated along carcinomas, depending on state, phenotype, malignancy grade.
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