Landscape of somatic mutations in sporadic GH-secreting XXXX .

@entity268 @entity2163 @entity5 @entity70834 @entity977 @entity701 @entity822 @entity460 @entity25946 @entity652
CONTEXT: Alterations in the @entity268 signaling pathway are common in hormonally active endocrine @entity5 . Somatic mutations at @entity2163 are causative in 30-40% of GH-secreting @entity652 . Recently, mutations affecting the @entity70834 and @entity25946 gene have been reported in ACTH-secreting @entity977 and @entity701 -secreting @entity822 respectively. However, the pathogenesis of many GH-secreting @entity652 remains unclear. AIM: Comprehensive genetic characterization of sporadic GH-secreting @entity652 and identification of new driver mutations. DESIGN: Screening for somatic mutations was performed in 67 GH-secreting @entity652 by targeted sequencing for @entity2163 , @entity25946 , and @entity70834 mutations (n=31) and next-generation exome sequencing (n=36). RESULTS: By targeted sequencing, known activating mutations in @entity2163 were detected in five cases (16.1%), while no somatic mutations were observed in both @entity25946 and @entity70834 . Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 @entity5 with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in @entity2163 (31.4% of cases). However, seven genes involved in @entity268 signaling pathway were affected in 14 of 36 samples and eight samples harbored variants in genes involved in the @entity460 signaling or metabolism. At the enrichment analysis, several altered genes resulted to be associated with developmental processes. No significant correlation between genetic alterations and the clinical data was observed. CONCLUSION: This study provides a comprehensive analysis of somatic mutations in a large series of GH-secreting @entity652 . No novel recurrent genetic alterations have been observed, but the data suggest that beside @entity268 pathway, @entity460 signaling might be involved in the pathogenesis of these @entity5 .
