Dataset Information

Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

ABSTRACT: Schwannomatosis (SWNTS) is a genetic cancer predisposition syndrome that manifests as multiple and often painful neuronal tumors called schwannomas (SWNs). While germline mutations in SMARCB1 or LZTR1, plus somatic mutations in NF2 and loss of heterozygosity in chromosome 22q have been identified in a subset of patients, little is known about the epigenomic and genomic alterations that drive SWNTS-related SWNs (SWNTS-SWNs) in a majority of the cases. We performed multiplatform genomic analysis and established the molecular signature of SWNTS-SWNs. We show that SWNTS-SWNs harbor distinct genomic features relative to the histologically identical non-syndromic sporadic SWNs (NS-SWNS). We demonstrate the existence of four distinct DNA methylation subgroups of SWNTS-SWNs that are associated with specific transcriptional programs and tumor location. We show several novel recurrent non-22q deletions and structural rearrangements. We detected the SH3PXD2A-HTRA1 gene fusion in SWNTS-SWNs, with predominance in LZTR1-mutant tumors. In addition, we identified specific genetic, epigenetic, and actionable transcriptional programs associated with painful SWNTS-SWNs including PIGF, VEGF, MEK, and MTOR pathways, which may be harnessed for management of this syndrome.

SUBMITTER: Mansouri S

PROVIDER: S-EPMC7785562 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

Mansouri Sheila S Suppiah Suganth S Mamatjan Yasin Y Paganini Irene I Liu Jeffrey C JC Karimi Shirin S Patil Vikas V Nassiri Farshad F Singh Olivia O Sundaravadanam Yogi Y Rath Prisni P Sestini Roberta R Gensini Francesca F Agnihotri Sameer S Blakeley Jaishri J Ostrow Kimberly K Largaespada David D Plotkin Scott R SR Stemmer-Rachamimov Anat A Ferrer Marcela Maria MM Pugh Trevor J TJ Aldape Kenneth D KD Papi Laura L Zadeh Gelareh G

Acta neuropathologica 20201006 1

Schwannomatosis (SWNTS) is a genetic cancer predisposition syndrome that manifests as multiple and often painful neuronal tumors called schwannomas (SWNs). While germline mutations in SMARCB1 or LZTR1, plus somatic mutations in NF2 and loss of heterozygosity in chromosome 22q have been identified in a subset of patients, little is known about the epigenomic and genomic alterations that drive SWNTS-related SWNs (SWNTS-SWNs) in a majority of the cases. We performed multiplatform genomic analysis a ...[more]

PMID: 33025139

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Dataset Information

Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

Publications

Epigenomic, genomic, and transcriptomic landscape of schwannomatosis.

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