Whole exome sequencing reveals that the majority of schwannomatosis cases remain unexplained after excluding SMARCB1 and LZTR1 germline variants

S Hutter, RM Piro, DE Reuss, V Hovestadt, F Sahm… - Acta …, 2014 - Springer
S Hutter, RM Piro, DE Reuss, V Hovestadt, F Sahm, S Farschtschi, H Kehrer-Sawatzki…
Acta neuropathologica, 2014Springer
Sonja Hutter· Rosario M. Piro· David E. Reuss· Volker Hovestadt· Felix Sahm· Said
Farschtschi· Hildegard Kehrer‑Sawatzki· Stephan Wolf· Peter Lichter· Andreas von Deimling·
Martin U. Schuhmann· Stefan M. Pfister· David TW Jones· Victor F. Mautner received: 16
May 2014/revised: 6 June 2014/Accepted: 16 June 2014/published online: 10 July 2014©
springer-Verlag Berlin Heidelberg 2014 familial and~ 10% of sporadic schwannomatosis
patients [4, 10, 12]. recently, another schwannomatosis-predisposing gene within the 22q …
Sonja Hutter· Rosario M. Piro· David E. Reuss· Volker Hovestadt· Felix Sahm· Said Farschtschi· Hildegard Kehrer‑Sawatzki· Stephan Wolf· Peter Lichter· Andreas von Deimling· Martin U. Schuhmann· Stefan M. Pfister· David TW Jones· Victor F. Mautner received: 16 May 2014/revised: 6 June 2014/Accepted: 16 June 2014/published online: 10 July 2014© springer-Verlag Berlin Heidelberg 2014 familial and~ 10% of sporadic schwannomatosis patients [4, 10, 12]. recently, another schwannomatosis-predisposing gene within the 22q candidate region has been identified. piotrowski et al.[9] reported germline loss-of-function mutations in LZTR1 in 80% of familial and sporadic schwannomatosis cases with combined chr22 loss and somatic NF2 mutation (MIM# 615670). LZTr1 functions as an adaptor of the cullin 3-containing e3 ubiquitin ligase complex and has recently been implicated in glioblastoma multiforme development [3], indicating a broader role in tumorigenesis. We therefore sought to further explore the prevalence of LZTR1 mutations in a cohort of 23 sporadic schwannomatosis patients. eight tumor-blood DNA pairs from de novo schwannomatosis patients were subjected to whole exome schwannomatosis (MIM# 162091) is characterized by the development of multiple schwannomas without vestibular nerve involvement (which is a characteristic of neurofibromatosis type 2—NF2—MIM# 101000). About 10% of patients have a family history of the disease, with the remaining 90% presumed to be sporadic [7]. Germline mutations of NF2 are not observed [8], although schwannomas frequently harbor somatic NF2 mutations and often display chromosome 22 loss [6]. rare cases with somatic mosaicism for NF2 alterations have also been described [5]. Germline mutations in SMARCB1 (INI1), located proximal to NF2 on chromosome 22, are found in~ 30–60% of
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