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Clinical Cancer Research Vol. 10, 8493-8500, December 15, 2004
© 2004 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Association of Epigenetic Inactivation of RASSF1A with Poor Outcome in Human Neuroblastoma

Qiwei Yang1, Peter Zage2, David Kagan1, Yufeng Tian1, Roopa Seshadri2, Helen R. Salwen1, Shuqing Liu1, Alexandre Chlenski1 and Susan L. Cohn2

1 The Robert H. Lurie Comprehensive Cancer Center and 2 Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois

Purpose: To investigate the prevalence and potential clinical significance of epigenetic aberrations in neuroblastoma (NB).

Experimental Design: The methylation status of 11 genes that are frequently epigenetically inactivated in adult cancers was assayed in 13 NB cell lines. The prevalence of RASSF1A and TSP-1 methylation was also analyzed in 56 NBs and 5 ganglioneuromas by methylation-specific PCR. Associations between the methylation status of RASSF1A and TSP-1 and patient age, tumor stage, tumor MYCN status, and patient survival were evaluated.

Results: Epigenetic changes were detected in all 13 NB cell lines, although the pattern of gene methylation varied. The putative tumor suppressor gene RASSF1A was methylated in all 13 cell lines, and TSP-1 and CASP8 were methylated in 11 of 13 cell lines. Epigenetic changes of DAPK and FAS were detected in only small numbers of cell lines, whereas none of the cell lines had methylation of p16, p21, p73, RAR2, SPARC, or TIMP-3. RASSF1A was also methylated in 70% of the primary NB tumors tested, and TSP-1 methylation was detected in 55% of the tumors. RASSF1A methylation was significantly associated with age >1 year (P < 0.01), high-risk disease (P < 0.016), and poor survival (P < 0.001). In contrast, no association between TSP-1 methylation and prognostic factors or survival was observed.

Conclusions: Our results suggest that epigenetic inactivation of RASSF1A may contribute to the clinically aggressive phenotype of high-risk NB.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.