PMID- 18559093
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20221207
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 7
DP  - 2008 Jun 17
TI  - Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals 
      target over-expressed genes, including Drosha.
PG  - 58
LID - 10.1186/1476-4598-7-58 [doi]
AB  - BACKGROUND: Copy number gains and amplifications are characteristic feature of 
      cervical cancer (CC) genomes for which the underlying mechanisms are unclear. 
      These changes may possess oncogenic properties by deregulating tumor-related 
      genes. Gain of short arm of chromosome 5 (5p) is the most frequent karyotypic 
      change in CC. METHODS: To examine the role of 5p gain, we performed a combination 
      of single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization 
      (FISH), and gene expression analyses on invasive cancer and in various stages of 
      CC progression. RESULTS: The SNP and FISH analyses revealed copy number increase 
      (CNI) of 5p in 63% of invasive CC, which arises at later stages of precancerous 
      lesions in CC development. We integrated chromosome 5 genomic copy number and 
      gene expression data to identify key target over expressed genes as a consequence 
      of 5p gain. One of the candidates identified was Drosha (RNASEN), a gene that is 
      required in the first step of microRNA (miRNA) processing in the nucleus. Other 
      5p genes identified as targets of CNI play a role in DNA repair and cell cycle 
      regulation (BASP1, TARS, PAIP1, BRD9, RAD1, SKP2, and POLS), signal transduction 
      (OSMR), and mitochondrial oxidative phosphorylation (NNT, SDHA, and NDUFS6), 
      suggesting that disruption of pathways involving these genes may contribute to CC 
      progression. CONCLUSION: Taken together, we demonstrate the power of integrating 
      genomics data with expression data in deciphering tumor-related targets of CNI. 
      Identification of 5p gene targets in CC denotes an important step towards 
      biomarker development and forms a framework for testing as molecular therapeutic 
      targets.
FAU - Scotto, Luigi
AU  - Scotto L
AD  - Department of Pathology, Columbia University Medical Center, New York, New York, 
      USA. ls339@columbia.edu
FAU - Narayan, Gopeshwar
AU  - Narayan G
FAU - Nandula, Subhadra V
AU  - Nandula SV
FAU - Subramaniyam, Shivakumar
AU  - Subramaniyam S
FAU - Kaufmann, Andreas M
AU  - Kaufmann AM
FAU - Wright, Jason D
AU  - Wright JD
FAU - Pothuri, Bhavana
AU  - Pothuri B
FAU - Mansukhani, Mahesh
AU  - Mansukhani M
FAU - Schneider, Achim
AU  - Schneider A
FAU - Arias-Pulido, Hugo
AU  - Arias-Pulido H
FAU - Murty, Vundavalli V
AU  - Murty VV
LA  - eng
GR  - R21 CA095647/CA/NCI NIH HHS/United States
GR  - CA095647/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20080617
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - EC 3.1.26.3 (DROSHA protein, human)
RN  - EC 3.1.26.3 (Ribonuclease III)
SB  - IM
MH  - Cell Line, Tumor
MH  - *Chromosomes, Human, Pair 5
MH  - Colombia
MH  - Disease Progression
MH  - Female
MH  - *Gene Amplification
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Genomics
MH  - Germany
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasm Invasiveness
MH  - New York
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polymorphism, Single Nucleotide
MH  - Precancerous Conditions/*genetics/pathology
MH  - Reproducibility of Results
MH  - Ribonuclease III/*genetics
MH  - Transcription, Genetic
MH  - Uterine Cervical Neoplasms/*genetics/pathology
MH  - Uterine Cervical Dysplasia/*genetics/pathology
PMC - PMC2440550
EDAT- 2008/06/19 09:00
MHDA- 2008/08/14 09:00
PMCR- 2008/06/17
CRDT- 2008/06/19 09:00
PHST- 2008/06/02 00:00 [received]
PHST- 2008/06/17 00:00 [accepted]
PHST- 2008/06/19 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/06/19 09:00 [entrez]
PHST- 2008/06/17 00:00 [pmc-release]
AID - 1476-4598-7-58 [pii]
AID - 10.1186/1476-4598-7-58 [doi]
PST - epublish
SO  - Mol Cancer. 2008 Jun 17;7:58. doi: 10.1186/1476-4598-7-58.