Evaluation of 1p36 markers and clinical outcome in a skull base chordoma study

¹ Department of Biology and Genetics, Medical Faculty, University of Milan, Milan, Italy
² Department of Neurosurgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
³ Department of Neurosurgery, University of Brescia, Brescia, Italy

^* To whom correspondence should be addressed. E-mail: paola.riva{at}unimi.it.

	Abstract

Chordomas are rare embryogenetic tumors, arising from remnants of the notochord, characterized by local invasiveness and variable tendency for recurrence. No molecular markers are currently used in a clinical setting to distinguish chordomas with an indolent or an aggressive pattern. Among the genetic lesions observed in this tumor, one of the most commonly detected is 1p loss. In a previous study we observed 1p36 loss of heterozygosity (LOH) in 85% of the analyzed chordomas. We studied a group of 16 homogeneously treated skull base chordomas (SBCs), reporting 1p36 LOH in 75% of them and determining the expression pattern of eight apoptotic genes mapped at 1p36. No tumors shared a common expression profile with nucleus pulposus, which is considered the only adult normal tissue deriving from notochord. In particular, tumor necrosis factor receptor superfamily genes TNFRSF8, TNFRSF9, and TNFRSF14 were differently expressed compared with control in a higher percentage of tumors (40%-53%) than were the remaining analyzed genes, suggesting that the deregulation of these three genes might have a role in chordoma tumorigenesis. The presence/absence of LOH and the expression/nonexpression of each apoptotic gene were studied in a survival analysis. Our results suggest that the lack of 1p36 LOH or the presence of TNFRSF8 expression might be associated with a better prognosis in patients with SBCs.

Key Words: 1p36 LOH, apoptotic gene, clinical outcome, expression profile, skull base chordoma

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