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

T Watanabe, A Vital, S Nobusawa, P Kleihues… - Acta …, 2009 - Springer
T Watanabe, A Vital, S Nobusawa, P Kleihues, H Ohgaki
Acta neuropathologica, 2009Springer
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 …
Abstract
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.
Springer