Universität zu Köln

Thompson, Daria, Vo, Kieuhoa T., London, Wendy B., Fischer, Matthias, Ambros, Peter F. ORCID: 0000-0002-5507-7211, Nakagawara, Akira, Brodeur, Garrett M., Matthay, Katherine K. and DuBois, Steven G. (2016). Identification of patient subgroups with markedly disparate rates of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group project. Cancer, 122 (6). S. 935 - 946. HOBOKEN: WILEY. ISSN 1097-0142

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Abstract

BACKGROUNDMYCN gene amplification (MNA) is a hallmark of aggressive neuroblastoma. This study was performed to determine univariate and multivariate predictors of tumor MNA. METHODSData from the International Neuroblastoma Risk Group were analyzed for a subset of 7102 patients with known MYCN status. Chi-square testing and logistic regression were used to identify univariate and multivariate predictors of MYCN status. Recursive partitioning was used to identify groups of patients with maximal differences in rates of MNA. RESULTSAll clinical features (age18 months, high ferritin levels, high lactate dehydrogenase [LDH] levels, International Neuroblastoma Staging System stage 4, and adrenal sites) and pathological/biological features (DNA index1, high mitosis-karyorrhexis index [MKI], undifferentiated/poorly differentiated grade, unfavorable histology according to the International Neuroblastoma Pathology Classification, and segmental chromosomal aberrations [SCAs]) were significantly associated with MNA. LDH (odds ratio [OR], 8.4; P<.001) and chromosomal 1p loss of heterozygosity (OR, 19.8; P<.001) were the clinical and biological variables, respectively, most strongly associated with MNA. In logistic regression, all variables except chromosome 17q aberration and pooled SCAs were independently predictive of MNA. Recursive partitioning identified subgroups with disparate rates of MNA, including subgroups with 85.7% MNA (patients with high LDH levels who had poorly differentiated adrenal tumors with chromosome 1p deletion) and 0.6% MNA (localized tumors having hyperdiploidy and low MKIs and lacking chromosome 1p aberrations). CONCLUSIONSMNA is strongly associated with other clinical and biological variables in neuroblastoma. Recursive partitioning has identified subgroups of neuroblastoma patients with highly disparate rates of MNA. These findings can be used to inform investigations of molecular mechanisms of MNA. Cancer 2016;122:935-45. (c) 2015 American Cancer Society. MYCN amplification in neuroblastoma is strongly associated with biology/pathology variables and particularly segmental chromosomal aberrations. Recursive partitioning techniques using these variables alone or in conjunction with clinical variables can identify subgroups of patients with markedly disparate rates of MYCN amplification.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thompson, Daria UNSPECIFIED UNSPECIFIED UNSPECIFIED Vo, Kieuhoa T. UNSPECIFIED UNSPECIFIED UNSPECIFIED London, Wendy B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Ambros, Peter F. UNSPECIFIED orcid.org/0000-0002-5507-7211 UNSPECIFIED Nakagawara, Akira UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodeur, Garrett M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthay, Katherine K. UNSPECIFIED UNSPECIFIED UNSPECIFIED DuBois, Steven G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281292
DOI:	10.1002/cncr.29848
Journal or Publication Title:	Cancer
Volume:	122
Number:	6
Page Range:	S. 935 - 946
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0142
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHILDRENS ONCOLOGY GROUP; N-MYC; METASTATIC NEUROBLASTOMA; GENE AMPLIFICATION; PROGNOSTIC-FACTORS; CHROMOSOME 1P; STAGE; AGE; DIAGNOSIS; DISEASE Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28129