Abstract
Integration of genome-wide profiles of DNA copy number alterations (CNAs) and gene expression variations (GEVs) could provide combined power to the identification of driver genes and gene networks in tumors. Here we merge matched genome and transcriptome microarray analyses from neuroblastoma samples to derive correlation patterns of CNAs and GEVs, irrespective of their genomic location. Neuroblastoma correlation patterns are strongly asymmetrical, being on average 10 CNAs linked to 1 GEV, and show the widespread prevalence of long range covariance. Functional enrichment and network analysis of the genes covarying with CNAs consistently point to a major cell function, the regulation of mitotic spindle assembly. Moreover, elevated expression of 14 key genes promoting this function is strongly associated to high-risk neuroblastomas with 1p loss and MYCN amplification in a set of 410 tumor samples (P <0.00001). Independent CNA/GEV profiling on neuroblastoma cell lines shows that increased levels of expression of these genes are linked to 1p loss. By this approach, we reveal a convergence of clustered neuroblastoma CNAs toward increased expression of a group of prognostic and functionally cooperating genes. We therefore propose gain of function of the spindle assembly machinery as a lesion potentially offering new targets for therapy of high-risk neuroblastoma.
| Original language | English |
|---|---|
| Pages (from-to) | 545-556 |
| Number of pages | 12 |
| Journal | Genes Chromosomes and Cancer |
| Volume | 51 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2012 |
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ASJC Scopus subject areas
- Cancer Research
- Genetics
Cite this
Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma. / Ooi, Wen Fong; Re, Angela; Sidarovich, Viktoryia; Canella, Valentina; Arseni, Natalia; Adami, Valentina; Guarguaglini, Giulia; Giubettini, Maria; Scaruffi, Paola; Stigliani, Sara; Lavia, Patrizia; Tonini, Gian Paolo; Quattrone, Alessandro.
In: Genes Chromosomes and Cancer, Vol. 51, No. 6, 06.2012, p. 545-556.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma
AU - Ooi, Wen Fong
AU - Re, Angela
AU - Sidarovich, Viktoryia
AU - Canella, Valentina
AU - Arseni, Natalia
AU - Adami, Valentina
AU - Guarguaglini, Giulia
AU - Giubettini, Maria
AU - Scaruffi, Paola
AU - Stigliani, Sara
AU - Lavia, Patrizia
AU - Tonini, Gian Paolo
AU - Quattrone, Alessandro
PY - 2012/6
Y1 - 2012/6
N2 - Integration of genome-wide profiles of DNA copy number alterations (CNAs) and gene expression variations (GEVs) could provide combined power to the identification of driver genes and gene networks in tumors. Here we merge matched genome and transcriptome microarray analyses from neuroblastoma samples to derive correlation patterns of CNAs and GEVs, irrespective of their genomic location. Neuroblastoma correlation patterns are strongly asymmetrical, being on average 10 CNAs linked to 1 GEV, and show the widespread prevalence of long range covariance. Functional enrichment and network analysis of the genes covarying with CNAs consistently point to a major cell function, the regulation of mitotic spindle assembly. Moreover, elevated expression of 14 key genes promoting this function is strongly associated to high-risk neuroblastomas with 1p loss and MYCN amplification in a set of 410 tumor samples (P <0.00001). Independent CNA/GEV profiling on neuroblastoma cell lines shows that increased levels of expression of these genes are linked to 1p loss. By this approach, we reveal a convergence of clustered neuroblastoma CNAs toward increased expression of a group of prognostic and functionally cooperating genes. We therefore propose gain of function of the spindle assembly machinery as a lesion potentially offering new targets for therapy of high-risk neuroblastoma.
AB - Integration of genome-wide profiles of DNA copy number alterations (CNAs) and gene expression variations (GEVs) could provide combined power to the identification of driver genes and gene networks in tumors. Here we merge matched genome and transcriptome microarray analyses from neuroblastoma samples to derive correlation patterns of CNAs and GEVs, irrespective of their genomic location. Neuroblastoma correlation patterns are strongly asymmetrical, being on average 10 CNAs linked to 1 GEV, and show the widespread prevalence of long range covariance. Functional enrichment and network analysis of the genes covarying with CNAs consistently point to a major cell function, the regulation of mitotic spindle assembly. Moreover, elevated expression of 14 key genes promoting this function is strongly associated to high-risk neuroblastomas with 1p loss and MYCN amplification in a set of 410 tumor samples (P <0.00001). Independent CNA/GEV profiling on neuroblastoma cell lines shows that increased levels of expression of these genes are linked to 1p loss. By this approach, we reveal a convergence of clustered neuroblastoma CNAs toward increased expression of a group of prognostic and functionally cooperating genes. We therefore propose gain of function of the spindle assembly machinery as a lesion potentially offering new targets for therapy of high-risk neuroblastoma.
UR - http://www.scopus.com/inward/record.url?scp=84859445266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859445266&partnerID=8YFLogxK
U2 - 10.1002/gcc.21940
DO - 10.1002/gcc.21940
M3 - Article
C2 - 22337647
AN - SCOPUS:84859445266
VL - 51
SP - 545
EP - 556
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
SN - 1045-2257
IS - 6
ER -