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Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas

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Abstract

Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade are required for cytokines, growth factors, G-proteins and hormones (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of cytokine signalling (SOCS) family of proteins. Their expression level is epigenetically regulated by DNA methylation. We have investigated the CpG island methylation status of SOCS-1 in a cohort of pituitary adenomas (PA; n=57), craniopharyngiomas (CP; n=30) and normal pituitary tissue (NP; n=11) using methylation sensitive single-strand conformation polymorphism analysis (MS-SSCP) and direct sequencing. SOCS-1 hypermethylation was identified in 51% (29/57) of surgical specimens obtained from PA patients. 83% of these tumours were clinically silent. In contrast, no methylation of SOCS-1 was observed in CPs or NPs. Quantitative real-time PCR and western blot analysis confirmed reduced SOCS-1 expression in the majority of pituitary adenomas. The data is compatible with epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK-STAT pathway in PA. This appears to contribute particularly to those tumours characterized by a hormone-inactive status.

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Acknowledgement

We kindly thank I. Jeske, D. Muller, I. Emtmann and B. Gillner for expert technical support. This work is supported by the Johannes and Frieda Marohn Foundation (RB and JK).

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Authors and Affiliations

  1. Department of Neuropathology, Friedrich-Alexander University of Erlangen-Nuremberg, Krankenhausstrasse 8-10, 91054, Erlangen, Germany

    Rolf Buslei, Verena Schmidt, Florian Siebzehnrübl & Ingmar Blümcke

  2. Department of Neurosurgery, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany

    Jürgen Kreutzer, Bernd Hofmann, Ilker Y. Eyupoglu & Rudolf Fahlbusch

  3. Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

    Eric Hahnen

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  1. Rolf Buslei
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Correspondence to Rolf Buslei.

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This work is supported by the Johannes and Frieda Marohn Foundation (RB and JK).

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Buslei, R., Kreutzer, J., Hofmann, B. et al. Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas. Acta Neuropathol 111, 264–271 (2006). https://doi.org/10.1007/s00401-005-0009-9

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