piwik-script

Intern
    Onkologische Forschung

    Panel-NGS in Adrenocortical Carcinoma

    Precision medicine in adrenocortical carcinoma – Molecular signature for prognostication and targeted therapy (collaboration among Endocrinology, Pathology, Human Genetics and Bioinformatics Unit CCC)

    Summary:

    Adrenocortical carcinoma (ACC) is a rare disease with poor prognosis and limited treatment options. This project aims to improve patient care by establishing a better prognostic score and identification of new drugable targets.

    Following first experience with exome sequencing in benign endocrine tumors (Beuschlein 2014, Reincke 2015, Calebiro 2016), we characterized (as part of two international consortia) large series of fresh frozen tumor material of ACC samples using comprehensive "multiple omic strategies" (Assie 2014, Zheng 2016). To apply these results for clinical use, we recently investigated the molecular signature of more than 100 formalin-fixed paraffin-embedded ACC tumor samples using targeted next generation sequencing (for mutations and copy number variations) and pyrosequencing (for methylation in promoter regions of selected genes). With this approach, we identified a restricted number of molecular alterations (i.e. total number of mutations, alterations in Wnt/β catenin and/or Rb/p53 pathways, and high methylation pattern) that might significantly improve the prognostic stratification of patients with ACC. In addition, we could pinpoint potential drugable events, which are particularly required for patients with advanced disease (manuscript in preparation).

    The current project aims to validate our ACC-specific combined score in an independent prospective series of patients by using a customized gene panel. Moreover, we intend to establish a reliable method for the isolation and sequencing of circulating tumor DNA for the early detection of disease recurrences (liquid biopsy). Our study will pave the way toward a precision medicine approach for patients with ACC.

    Recent Publications

    Plasma steroid metabolome profiling for the diagnosis of adrenocortical carcinoma.
    Schweitzer S, Kunz M, Kurlbaum M, Vey J, Kendl S, Deutschbein T, Hahner S, Fassnacht M, Dandekar T, Kroiss M.
    Eur J Endocrinol. 2019 Feb 1;180(2):117-125. doi: 10.1530/EJE-18-0782.

    Advanced Adrenocortical Carcinoma - What to do when First-Line Therapy Fails?
    Megerle F, Kroiss M, Hahner S, Fassnacht M.
    Exp Clin Endocrinol Diabetes. 2019 Feb;127(2-03):109-116. doi: 10.1055/a-0715-1946.

    Patterns of Lymph Node Recurrence in Adrenocortical Carcinoma: Possible Implications for Primary Surgical Treatment.
    Reibetanz J, Rinn B, Kunz AS, Flemming S, Ronchi CL, Kroiss M, Deutschbein T, Pulzer A, Hahner S, Kocot A, Germer CT, Fassnacht M, Jurowich C. 
    Ann Surg Oncol. 2019 Feb;26(2):531-538. doi: 10.1245/s10434-018-6999-z.

    Hsp90 inhibition in adrenocortical carcinoma: Limited drug synergism with mitotane.
    Sbiera S, Kendl S, Weigand I, Sbiera I, Fassnacht M, Kroiss M.
    Mol Cell Endocrinol. 2019 Jan 15;480:36-41. doi: 10.1016/j.mce.2018.10.009.

    Advanced Adrenocortical Carcinoma - What to do when First-Line Therapy Fails? 
    Megerle F, Kroiss M, Hahner S, Fassnacht M.
    Exp Clin Endocrinol Diabetes. 2019 Feb;127(2-03):109-116. doi: 10.1055/a-0715-1946

    Treatment of Refractory Adrenocortical Carcinoma with Thalidomide: Analysis of 27 Patients from the European Network for the Study of Adrenal Tumours Registry.
    Kroiss M, Deutschbein T, Schlötelburg W, Ronchi CL, Hescot S, Körbl D, Megerle F, Beuschlein F, Neu B, Quinkler M, Baudin E, Hahner S, Heidemeier A, Fassnacht M.
    Exp Clin Endocrinol Diabetes. 2018 Nov 14. doi: 10.1055/a-0747-5571.

    Influence of hormonal functional status on survival in adrenocortical carcinoma: systematic review and meta-analysis.
    Vanbrabant T, Fassnacht M, Assie G, Dekkers OM.
    Eur J Endocrinol. 2018 Dec 1;179(6):429-436. doi: 10.1530/EJE-18-0450

    European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors
    Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R, Haak HR, Mihai R, Assie G, Terzolo M.
    Eur J Endocrinol. 2018 Oct 1;179(4):G1-G46. doi: 10.1530/EJE-18-0608.

    Targeted Molecular Analysis in Adrenocortical Carcinomas: A Strategy Toward Improved Personalized Prognostication.
    Lippert J, Appenzeller S, Liang R, Sbiera S, Kircher S, Altieri B, Nanda I, Weigand I, Gehrig A, Steinhauer S, Riemens RJM, Rosenwald A, Müller CR, Kroiss M, Rost S, Fassnacht M, Ronchi CL.
    J Clin Endocrinol Metab. 2018 Dec 1;103(12):4511-4523. doi: 10.1210/jc.2018-01348.

    Enzyme autoinduction by mitotane supported by population pharmacokinetic modelling in a large cohort of adrenocortical carcinoma patients.
    Arshad U, Taubert M, Kurlbaum M, Frechen S, Herterich S, Megerle F, Hamacher S, Fassnacht M, Fuhr U, Kroiss M.
    Eur J Endocrinol. 2018 Oct 16;179(5):287-297. doi: 10.1530/EJE-18-0342

    Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma.
    Megerle F, Herrmann W, Schloetelburg W, Ronchi CL, Pulzer A, Quinkler M, Beuschlein F, Hahner S, Kroiss M, Fassnacht M; German ACC Study Group.
    J Clin Endocrinol Metab. 2018 Apr 1;103(4):1686-1695. doi: 10.1210/jc.2017-02591.

    ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas.
    Laufs V, Altieri B, Sbiera S, Kircher S, Steinhauer S, Beuschlein F, Quinkler M, Willenberg HS, Rosenwald A, Fassnacht M, Ronchi CL.
    Eur J Endocrinol. 2018 Feb;178(2):181-188. doi: 10.1530/EJE-17-0788.