Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma

Rosty, Christophe, Sheffer, Michal, Tsafrir, Dafna, Stransky, Nicolas, Tsafrir, Ilan, Peter, Martine, de Cremoux, Patricia, de La Rochefordiere, Anne, Salmon, Remy, Dorval, Thierry, Thiery, Jean Paul, Couturier, Jerome, Radvanyi, Francois, Domany, Eytan and Sastre-Garau, Xavier (2005) Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma. Oncogene, 24 47: 7094-7104. doi:10.1038/sj.onc.1208854


Author Rosty, Christophe
Sheffer, Michal
Tsafrir, Dafna
Stransky, Nicolas
Tsafrir, Ilan
Peter, Martine
de Cremoux, Patricia
de La Rochefordiere, Anne
Salmon, Remy
Dorval, Thierry
Thiery, Jean Paul
Couturier, Jerome
Radvanyi, Francois
Domany, Eytan
Sastre-Garau, Xavier
Title Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2005-10
Sub-type Article (original research)
DOI 10.1038/sj.onc.1208854
Volume 24
Issue 47
Start page 7094
End page 7104
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Specific HPV DNA sequences are associated with more than 90% of invasive carcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators in cell transformation by disrupting TP53 and RB pathways. To investigate molecular mechanisms involved in the progression of invasive cervical carcinoma, we performed a gene expression study on cases selected according to viral and clinical parameters. Using Coupled Two-Way Clustering and Sorting Points Into Neighbourhoods methods, we identified a ‘cervical cancer proliferation cluster’ composed of 163 highly correlated transcripts. Most of these transcripts corresponded to E2F pathway genes controlling cell division or proliferation, whereas none was known as TP53 primary target. The average expression level of the genes of this cluster was higher in tumours with an early relapse than in tumours with a favourable course (P=0.026). Moreover, we found that E6/E7 mRNA expression level was positively correlated with the expression level of the cluster genes and with viral DNA load. These findings suggest that HPV E6/E7 expression level plays a key role in the progression of invasive carcinoma of the uterine cervix via the deregulation of cellular genes controlling tumour cell proliferation. HPV expression level may thus provide a biological marker useful for prognosis assessment and specific therapy of the disease.
Keyword Cervical cancer
Gene expression
HPV
Prognosis
Bioinformatics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 68 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 79 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 09 Mar 2011, 14:23:14 EST