Universität zu Köln

Coco, Simona ORCID: 0000-0002-5296-4325, Theissen, Jessica, Scaruffi, Paola, Stigliani, Sara ORCID: 0000-0001-5115-2520, Moretti, Stefano, Oberthuer, Andre, Valdora, Francesca, Fischer, Matthias, Gallo, Fabio, Hero, Barbara, Bonassi, Stefano ORCID: 0000-0003-3833-6717, Berthold, Frank and Tonini, Gian Paolo (2012). Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma. Int. J. Cancer, 131 (7). S. 1591 - 1601. HOBOKEN: WILEY. ISSN 1097-0215

Full text not available from this repository.

Abstract

About 50% of children with neuroblastoma (NB) show a metastatic disease and have a poor prognosis. However, disease progression is greatly variable and depends on patients' age and MYCN oncogene amplification. To investigate the role of patients' age in tumor aggressiveness, we performed array-CGH and gene expression profiles of three groups (G) of metastatic NBs: G1, stage 4S patients and MYCN single copy (MYCN-) tumors; G2, stage 4 patients, =18 months of age, MYCN- tumors and favorable outcome and G3, Stage 4 patients, =19 months with unfavorable outcome. G1 was characterized by numerical aberrations prevalently; on the contrary, all G3 tumors had structural rearrangements, whereas G2 showed an intermediate pattern. The average of numerical alterations decreased significantly from G1 to G2 to G3 (p < 0.01). Contrarily, the number of structural aberrations increased from G1 to G2 to G3 (p < 2.35 E-05). Noteworthy, G3/MYCN- NBs were characterized by several complex intrachromosome rearrangements. Expression analysis of the three groups showed significant differences in genes of Rho and Ras signaling pathways, development and adhesion, cell cycle regulation and telomerase activity. Accumulation of structural alterations increased with patients' age and was associated with a more aggressive disease. Abnormal expression of genes involved in cell cycle and telomerase in G3 may be responsible for the genomic instability in this cohort of patients. The higher DNA instability observed in G3/MYCN- NBs than in MYCN-amplified G3 may also explain why patients =19 months have a poor outcome independently by MYCN status.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Coco, Simona UNSPECIFIED orcid.org/0000-0002-5296-4325 UNSPECIFIED Theissen, Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Scaruffi, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Stigliani, Sara UNSPECIFIED orcid.org/0000-0001-5115-2520 UNSPECIFIED Moretti, Stefano UNSPECIFIED UNSPECIFIED UNSPECIFIED Oberthuer, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Valdora, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Gallo, Fabio UNSPECIFIED UNSPECIFIED UNSPECIFIED Hero, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonassi, Stefano UNSPECIFIED orcid.org/0000-0003-3833-6717 UNSPECIFIED Berthold, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Tonini, Gian Paolo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482440
DOI:	10.1002/ijc.27432
Journal or Publication Title:	Int. J. Cancer
Volume:	131
Number:	7
Page Range:	S. 1591 - 1601
Date:	2012
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CDNA MICROARRAY DATA; EXPRESSION-BASED CLASSIFICATION; CHROMOSOME ARM 17Q; HUMAN CANCERS; PROGNOSIS; TUMORS; RISK; IDENTIFICATION; NORMALIZATION; 1P Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48244