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  • Oxford University Press (OUP)  (2)
  • Ronchi, Cristina L  (2)
  • 1
    Online Resource
    Online Resource
    Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas
    Oxford University Press (OUP) ; 2016
    In:  European Journal of Endocrinology Vol. 174, No. 3 ( 2016-03), p. 363-372
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 174, No. 3 ( 2016-03), p. 363-372
    Abstract: Alterations in the cAMP signaling pathway are common in hormonally active endocrine tumors. Somatic mutations at GNAS are causative in 30–40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical adenomas respectively. However, the pathogenesis of many GH-secreting adenomas remains unclear. Aim Comprehensive genetic characterization of sporadic GH-secreting adenomas and identification of new driver mutations. Design Screening for somatic mutations was performed in 67 GH-secreting adenomas by targeted sequencing for GNAS , PRKACA , and USP8 mutations ( n =31) and next-generation exome sequencing ( n =36). Results By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8 . Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1–13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight samples harbored variants in genes involved in the calcium 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 adenomas. No novel recurrent genetic alterations have been observed, but the data suggest that beside cAMP pathway, calcium signaling might be involved in the pathogenesis of these tumors.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-15-1064
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1485160-X
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  • 2
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    Online Resource
    Performance of DNA-based biomarkers for classification of adrenocortical carcinoma: a prognostic study
    Oxford University Press (OUP) ; 2023
    In:  European Journal of Endocrinology Vol. 189, No. 2 ( 2023-08-02), p. 262-270
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 189, No. 2 ( 2023-08-02), p. 262-270
    Abstract: Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with heterogeneous clinical outcomes. Recent studies proposed a combination of clinical/histopathological parameters (S-GRAS score) or molecular biomarkers (BMs) to improve prognostication. We performed a comparative analysis of DNA-based BMs by evaluating their added prognostic value to the S-GRAS score. Design and methods A total of 194 formalin-fixed, paraffin-embedded (FFPE) ACC samples were analysed, including a retrospective training cohort (n = 107) and a prospective validation cohort (n = 87). Targeted DNA sequencing and pyrosequencing were used to detect somatic single-nucleotide variations in ACC-specific genes and methylation in the promoter region of paired box 5 (PAX5). The European Network for the Study of Adrenocortical Tumors (ENSAT) tumour stage, age, symptoms at presentation, resection status, and Ki-67 were combined to calculate S-GRAS. Endpoints were overall (OS), progression-free (PFS), and disease-free survival (DFS). Prognostic role was evaluated by multivariable survival analysis and their performance compared by Harrell's concordance index (C index). Results In training cohort, an independent prognostic role was confirmed at multivariate analysis for two DNA-based BMs: alterations in Wnt/β-catenin and Rb/p53 pathways and hypermethylated PAX5 (both P & lt; .05 for PFS and DFS, hazard ratio [HR] 1.47-2.33). These were combined to S-GRAS to obtain a combined (COMBI) score. At comparative analysis, the best discriminative prognostic model was COMBI score in both cohorts for all endpoints, followed by S-GRAS score (C index for OS 0.724 and 0.765, PFS 0.717 and 0.670, and DFS 0.699 and 0.644, respectively). Conclusions Targeted DNA-based BM evaluated on routinely available FFPE samples improves prognostication of ACC beyond routinely available clinical and histopathological parameters. This approach may help to better individualise patient's management.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1093/ejendo/lvad112
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1485160-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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