Genetic and Expression Profiles of Cerebellar Liponeurocytomas

Abstract

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or beta-catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Cerebellar Liponeurocytoma

“…The MIB-1 (Ki-67) labeling index is typically between 1% and 3% but may be higher. 10,11 Ultrastructural studies have confirmed large, nonmembrane-bound lipid deposits within the cytoplasm of tumor cells. Such cells nevertheless retain features of neuronal differentiation, including dense core neurosecretory granules, microtubules, and synaptic junctions containing clear vesicles.…”

“…Due to the paucity of long-term follow-up data, it is unclear whether radiation should be given in the immediate postoperative period or be reserved for recurrent tumor, which may occur many years following initial surgery. 10,11 When administered, radiotherapy is generally limited to the posterior fossa. 5 No cases of spinal …”

“…In one collective series, 6 of 15 patients (40%) with available follow-up information had recurrence during a period ranging from 1 to 12 years. 10 Recurrent tumors may display increased mitotic activity, increased proliferative activity as assessed by MIB-1 staining, vascular proliferation, and necrosis. [18][19][20] However, some tumors recur in the absence of such atypical histopathologic features.…”

Neuronal and Mixed Neuronal-Glial Tumors of the Central Nervous System

“…These data suggest that central neurocytomas are genetically distinct from oligodendrogliomas. Although the expression profiles of cerebellar liponeurocytomas appear to have a closer relationship to those of central neurocytomas, the lack of TP53 mutations in central neurocytomas suggests the involvement of different genetic pathways (60,66,67).…”

“…In the 29 patients with cerebellar liponeurocytoma reported ( 182,185,186,187,188,189), the mean age was around 50 years (range, 24-77 years), with a peak in the third to sixth decade of life. This is in contrast with the age distribution of cerebellar medulloblastomas, more than 70% of which occur in children (178).…”