Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

Abstract

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies.

Novel amplifications in pediatric medulloblastoma identified by genome-wide copy number profiling

“…In agreement with our results, the association of 17q gain with poor outcome could not be verified by a recent immunohistochemistry analysis of 207 MB samples [54], and neither did pooled analysis of chromosomal copy number aberration data identify isodicentric chromosome 17 as prognostically significant in MB [55]. It has been suggested that the discrepancy between studies may depend on the proportion of WNT tumors included in individual cohorts.…”

Chromosomal heterogeneity and instability characterize pediatric medulloblastoma cell lines and affect neoplastic phenotype

“…Some CCAs have also been proposed as independent prognostic markers and determinants of new MB subtypes (Lamont et al 2004;Gilbertson and Ellison 2008;McCabe et al 2011). Here, we identified many numerical and structural alterations in both cell lines evaluated, mainly chromosomal gain and structural rearrangement of chromosome 1 and 7.…”

Analysis of Chromosome 17 miRNAs and Their Importance in Medulloblastomas

“…This group of patients with anaplastic MB and loss of chromosome 17 has lower survival rates than patients without loss of this chromosome. Afterwards, it was shown that chromosome 17 and its alterations are important markers to stratify patients with respect to their prognosis [ 8 ].…”

“…The gain of 17q without loss of 17p showed a tendency to better prognosis. The careful analysis of all data suggested that, in general, the loss of 17p is a marker of poor prognosis, while the gain of 17q might be a new marker of good prognosis in patients with MB [ 8 ].…”