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Comprehensive genetic and histopathologic study reveals three types of neuroblastoma tumors

Lookup NU author(s): Dr Maria Lastowska, Simon Cotterill, Dr Nicholas Bown, Dr Katia Mazzocco, Professor Andrew Pearson, Dr Michael Jackson


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Purpose: To determine the relationship between multiple genetic features, tumor morphology, and prognosis in neuroblastoma. Patients and Methods: The genetic alterations and morphologic features that underpin three histopathologic risk classifications were analyzed in 108 neuroblastoma patients. Tumors were subdivided into four groups based on the three most frequent and prognostically significant genetic alterations (17q gain, 1p deletion, and MYCN amplification), and all other genetic, morphologic, and clinical data were analyzed with respect to these groups. Results: Our analyses identify three nonoverlapping tumor types with distinct genetic and morphologic features, defined here as types 1, 2, and 3. Type 1 tumors show none of the three significant genetic alterations and have good prognosis. Both type 2 (17q gain only or 17q gain and 1p del) and type 3 (17q gain, 1p del, and MYCN amplification) tumors progress. However, these tumor types are distinguished clinically by having significantly different median age at diagnosis and median progression-free survival (PFS). Multivariate analysis indicates that 17q gain is the only independent prognostic factor among all genetic, histopathologic, and clinical factors analyzed. Among histopathologic risk systems, the International Neuroblastoma Pathology Classification was the best predictor of PFS. Conclusion: Our results indicate that specific combinations of genetic changes in neuroblastoma tumors contribute to distinct morphologic and clinical features. Furthermore, the identification of two genetically and morphologically distinct types of progressing tumors suggests that possibilities for different therapeutic regimens should be investigated. J Clin Oncol 19:3080-3090. (C) 2001 by American Society of Clinical Oncology.

Publication metadata

Author(s): Lastowska MA, Cullinane C, Variend S, Cotterill SJ, Bown NP, O'Neill S, Mazzocco K, Roberts P, Nicholson J, Ellershaw C, Pearson ADJ, Jackson MS

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Oncology

Year: 2001

Volume: 19

Issue: 12

Pages: 3080-3090

ISSN (print): 0732-183X

ISSN (electronic): 1527-7755


PubMed id: 11408505