Abstract
IDH mutations are found in the majority of adult, diffuse, low-grade and anaplastic gliomas and are also frequently found in cartilaginous tumors. Ollier disease and Maffucci syndrome are two enchondromatosis syndromes characterized by the development of multiple benign cartilaginous tumors due to post-zygotic acquisition of IDH mutations. In addition to skeletal tumors, enchondromatosis patients sometimes develop gliomas. The aim of the present study was to determine whether gliomas in enchondromatosis patients might also result from somatic IDH mosaicism and whether their characteristics are similar to those of sporadic IDH-mutated gliomas. For this purpose, we analyzed the characteristics of 6 newly diagnosed and 32 previously reported cases of enchondromatosis patients who developed gliomas and compared them to those of a consecutive series of 159 patients with sporadic IDH-mutated gliomas. As was the case with sporadic IDH mutated gliomas, enchondromatosis gliomas were frequently located in the frontal lobe (54 %) and consisted of diffuse low-grade (73 %) or anaplastic gliomas (21 %). However, they were diagnosed at an earlier age (25.6 years versus 44 years, p < 0.001) and were more frequently multicentric (32 % versus 1 %, p < 0.001) and more frequently located within the brainstem than sporadic IDH mutated gliomas (21 % versus 1 %, p < 0.001). Their molecular profile was characterized by IDH mutations and loss of ATRX expression. In two patients, the same IDH mutation was demonstrated in the glioma and in a cartilaginous tumor. In contrast to sporadic IDH mutated gliomas, no enchondromatosis glioma harbored a 1p/19q co-deletion (0/6 versus 59/123, p = 0.03). The characteristics of gliomas in patients with enchondromatosis suggest that these tumors, as cartilaginous tumors, result from somatic IDH mosaicism and that the timing of IDH mutation acquisition might affect the location and molecular characteristics of gliomas. Early acquisition of IDH mutations could shift gliomagenesis towards the brainstem thereby mimicking the regional preference of histone mutated gliomas.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0302-y) contains supplementary material, which is available to authorized users.
Highlights
Mutations in the IDH1 or IDH2 genes are found in the majority of adult diffuse grade II and grade III gliomas and are considered as the earliest oncogenic event in these tumors [50]
Materials and methods We retrospectively reviewed the medical and radiological records of 6 patients with Ollier disease (n = 5) or Maffucci syndrome (n = 1) who were referred to our neuro-oncology departments (Pitié-Salpêtière Hospital in Paris, Hospices Civils of Lyon, CHU of Bordeaux and Rennes) for the diagnosis of glioma, as well as 159 consecutive patients who were diagnosed with an IDH1 or IDH2 mutated sporadic glioma between 2010 and 2014 (Hospices Civils of Lyon)
The diagnosis of Ollier disease (n = 28) or Maffucci syndrome (n = 10) was made during childhood based on the occurrence of multiple enchondromas predominating on the articulations of the knees, hands and toes
Summary
Mutations in the IDH1 or IDH2 genes are found in the majority of adult diffuse grade II and grade III gliomas and are considered as the earliest oncogenic event in these tumors [50]. These mutations result in the abnormal production of 2-hydroxyglutarate (2-HG) which is structurally similar to alpha-ketoglutarate. The aim of the present study was to determine whether gliomas in enchondromatosis patients might result from somatic IDH mosaicism and whether their characteristics are similar to those of sporadic IDH-mutated gliomas. We analyzed the characteristics of 6 newly diagnosed and 32 previously reported cases of enchondromatosis patients who developed gliomas, and compared them to those of a consecutive series of 159 patients with sporadic IDH-mutated gliomas
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