Diffuse intrinsic pontine tumors: a study of primitive neuroectodermal tumors versus the more common diffuse intrinsic pontine gliomas.
ABSTRACT The diagnosis of diffuse pontine tumors has largely been made on the basis of MRI since the early 1990 s. In cases of tumors considered "typical," as a rule, no biopsy specimen has been obtained, and the tumors have been considered diffuse intrinsic pontine gliomas (DIPGs). There have been sporadic reports that primitive neuroectodermal tumors (PNETs) of the pons may not be distinguishable from the DIPGs by radiological imaging. This study presents 2 cases of diffuse pontine PNETs with molecular evidence that these are indeed PNETs, distinct from DIPGs, thus supporting biopsy of diffuse pontine tumors as a standard of care.
Biopsy specimens were obtained from 7 diffuse pontine tumors and snap frozen. Two of these 7 tumors were identified on the basis of pathological examination as PNETs. All 7 of the diffuse pontine tumors were analyzed for gene expression using the Affymetrix HG-U133 Plus 2.0 GeneChip microarray. Gene expression was compared with that of supratentorial PNETs, medulloblastomas, and low- and high-grade gliomas outside the brainstem.
Unsupervised hierarchical clustering analysis of gene expression demonstrated that pontine PNETs are most closely related to PNETs of the supratentorial region and not with gliomas. They do not cluster with the 5 DIPGs in the study. Thirty-eight genes, including GATA3, are uniquely differentially expressed in pontine PNETs compared with other types of pediatric brain tumors, including DIPGs and other PNETs at a false discovery rate statistical significance of less than 0.05.
The cluster and individual gene expression analyses indicate that pontine PNETs are intrinsically different from DIPGs. The 2 pontine PNET cases cluster with supratentorial PNETs, rather than with DIPGs, suggesting that these tumors should be treated with a PNET regimen, not with DIPG therapy. Since diagnosis by imaging is not reliable and the biology of the tumors is disparate, a biopsy should be performed to enable accurate diagnosis and direct potentially more effective treatments.
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ABSTRACT: Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.Nature 02/2002; 415(6870):436-42. · 38.60 Impact Factor
- Acta Neuropathologica 12/2011; 122(6):783-5. · 9.73 Impact Factor
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ABSTRACT: The diagnosis of brainstem glioma was long considered a single entity. However, since the advent of magnetic resonance imaging in the late 1980s, neoplasms within this anatomic region are now recognized to include several tumors of varying behavior and natural history. More recent reports of brainstem tumors include diverse sites such as the cervicomedullary junction, pons, midbrain, or the tectum. Today, these tumors are broadly categorized as either diffuse intrinsic gliomas, most often in the pons, or the nondiffuse brainstem tumors originating at the tectum, focally in the midbrain, dorsal and exophytic to the brainstem, or within the cervicomedullary junction. Although we briefly discuss the nondiffuse tumors, we focus specifically on those diffuse brainstem tumors that regrettably still carry a bleak prognosis.Journal of Clinical Oncology 04/2006; 24(8):1266-72. · 18.04 Impact Factor