Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome

• DOI: 10.1007/s00401-009-0528-x
• Publication Date: 2009-04-01T04:40:50Z
• Authors: Takuya Watanabe; Anne Vital; Sumihito Nobusawa; Paul Kleihues; Hiroko Ohgaki
• Keywords: Li–Fraumeni syndrome

Mutations of the IDH1 gene are frequent in gliomas, with R132H (CGT-->CAT) being the most common (>85%). In astrocytomas, IDH1 mutations are typically co-present with, or precede, TP53 mutations. We assessed IDH1 mutations in brain tumors diagnosed in patients from three families with Li-Fraumeni syndrome. We identified IDH1 mutations in five astrocytomas that developed in carriers of a TP53 germline mutation. Without exception, all were R132C (CGT-->TGT), which in sporadic astrocytomas accounts for <5% of IDH1 mutations. This remarkably selective occurrence of R132C mutations may reflect differences in the sequence of genetic events, with a preference for R132C mutations in astrocytes or precursor cells that already carry a germline TP53 mutation.