Identification of low intratumoral gene expression heterogeneity in neuroblastic tumors by genome-wide expression analysis and Game Theory

被引：55

作者：

Albino, Domenico ^{[2
]}

Scaruffi, Paola ^{[1
]}

Moretti, Stefano

Coco, Simona ^{[1
]}

Truini, Mauro ^{[3
]}

Di Cristofano, Claudio ^{[4
]}

Cavazzana, Andrea ^{[5
]}

Stigliani, Sara ^{[1
]}

Bonassi, Stefano

Tonini, Gian Paolo ^{[1
]}

机构：

[1] Natl Canc Res Inst IST, I-16132 Genoa, Italy

[2] Natl Inst Canc Res, Lab Italian Neuroblastoma Fdn, Genoa, Italy

[3] Natl Inst Canc Res, Dept Pathol, Genoa, Italy

[4] Univ Roma La Sapienza, Dept Expt Med, Latina, Italy

[5] Azienda Sanitaria Locale N 1, Dept Oncol, Unit Surg Pathol, Carrara, Italy

来源：

CANCER | 2008年 / 113卷 / 06期

关键词：

neuroblastic tumors; Schwannian cells; microarray; laser capture microdissection; Game Theory;

D O I：

10.1002/cncr.23720

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND. Neuroblastic tumors (NTs) are largely comprised of neuroblastic (Nb) cells with various quantities of Schwannian stromal (SS) cells. NTs show a variable genetic heterogeneity. NT gene expression profiles reported so far have not taken into account the cellular components. The authors reported the genome-wide expression analysis of whole Minors and microdissected Nb and SS cells. METHODS. The authors analyzed gene expression profiles of 10 stroma-poor NTs (NTs-SP) and 9 stroma-rich NTs (NTS-SR) by microarray technology. Nb and SS cells were. isolated by laser microdissection from NTs-SP and NTs-SR and probed with microarrays. Gene expression data were analyzed by the Significance Analysis of Microarrays (SAM) and Game Theory (GT) methods, the latter applied for the first time to microarray data evaluation. RESULTS. SAM identified 84 genes differentially expressed between NTs-SP and NTs-SR, whereas 50 were found by GT. NTs-SP mainly express genes associated with cell replication, nervous system development, and antiapoptotic pathways, whereas NTs-SR express genes of cell-cell communication and apoptosis. Combining SAM and GT, the authors found 16 common genes driving the separation between NTs-SP and NTs-SR. Five genes overexpressed in NTs-SP encode for nuclear proteins (CENPE, EYA1, PBK TOP2A, TFAP2B), whereas only 1 of 11 highly expressed genes in NTs-SR encodes for a nuclear receptor (NR4A2). CONCLUSIONS. The results showed that NT-SP and NT-SR gene signatures differ for a set of genes involved in distinct pathways, and the authors demonstrated a low intratumoral heterogeneity at the mRNA level in both NTs-SP and NTs-SR. The combination of SAM and GT methods may help to better identify gene expression profiling in NTs.

引用

页码：1412 / 1422

页数：11

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