GENE-02. GERMLINE MUTATIONS WITHIN THE SWI/SNF COMPLEX PREDICT PATIENTS’ AGE OF ONSET AND TYPE OF DISEASE

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2017-06, Vol.19 (suppl_4), p.iv18-iv18
• Main Authors: Holsten, Till, Hasselblatt, Martin, Kordes, Uwe, Siebert, Reiner, Schneppenheim, Reinhard, Frühwald, Michael, Schüller, Ulrich
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nox083.073

Germline mutations affecting the SWI/SNF chromatin remodeling complex are associated with a broad spectrum of different diseases, including malignant and benign tumors as well as neurodevelopmental disorders. Such mutations are detected in multiple genes of the complex and encompass a variety of mutation types. However, due to the rarity of mutation carriers, very little is known about the impact of specific SWI/SNF mutations on the phenotype of the affected individual. In this meta-analysis, we link genetic and clinical data from more than 400 families and more than 500 patients affected by SWI/SNF germline alterations, including over 40 so far unpublished patients. Here we demonstrate that large deletions and truncating mutations of a gene tend to be associated with malignancy and early-onset-disease, while non-truncating mutations may cause non-malignant disorders, such as Coffin-Siris-syndrome or late onset tumors like Schwannomas or Meningiomas (p=