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The genomics of pilocytic astrocytoma formation in neurofibromatosis type 1

ABSTRACT:

Neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome is one of the most common autosomal dominant tumor predisposition syndromes in which affected individuals develop brain tumors. These low-grade glial neoplasms (pilocytic astrocytomas) typically arise in children younger than 7 years of age and are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. In this study, whole genome sequence analysis was performed on three NF1-associated pilocytic astrocytoma tumors (NF1-PA) and matched normal blood samples to establish the genomic landscape of NF1-PA. These data support the existence of multiple distinct mechanisms (mutation, LOH, and methylation) underlying somatic NF1 inactivation in NF1-PA tumors.

PROVIDER: phs000563.v1.p1 | EGA |

REPOSITORIES: EGA

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Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma.

Gutmann David H DH McLellan Michael D MD Hussain Ibrahim I Wallis John W JW Fulton Lucinda L LL Fulton Robert S RS Magrini Vincent V Demeter Ryan R Wylie Todd T Kandoth Cyriac C Leonard Jeffrey R JR Guha Abhijit A Miller Christopher A CA Ding Li L Mardis Elaine R ER

Genome research 20121205 3

Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological featur ...[more]

PMID: 23222849

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Pilocytic Astrocytoma in NF1

Project description:<p>Neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome is one of the most common autosomal dominant tumor predisposition syndromes in which affected individuals develop brain tumors. These low-grade glial neoplasms (pilocytic astrocytomas) typically arise in children younger than 7 years of age and are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. In this study, whole genome sequence analysis was performed on three NF1-associated pilocytic astrocytoma tumors (NF1-PA) and matched normal blood samples to establish the genomic landscape of NF1-PA. These data support the existence of multiple distinct mechanisms (mutation, LOH, and methylation) underlying somatic NF1 inactivation in NF1-PA tumors.</p>

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