dorsal/arxiv
View SchemaIdentification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma
| Authors | Christophe Rosty, Michal Sheffer, Dafna Tsafrir, Nicolas Stransky, Ilan Tsafrir, Martine Peter, Patricia de Cremoux, Anne de La Rochefordiere, Remy Salmon, Thierry Dorval, Jean Paul Thiery, Jerome Couturier, Francois Radvanyi, Eytan Domany, Xavier Sastre-Garau |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0511019 |
| URL | https://arxiv.org/abs/q-bio/0511019 |
| Journal | Oncogene vol 24, p 7094-7104 (2005) |
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, many of which corresponded to E2F pathway genes controlling cell proliferation, whereas no primary TP53 targets were present in this cluster. 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 correspond to a biological marker useful for prognosis assessment and specific therapy of the disease.
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"abstract": "Specific HPV DNA sequences are associated with more than 90% of invasive\ncarcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators\nin cell transformation by disrupting TP53 and RB pathways. To investigate\nmolecular mechanisms involved in the progression of invasive cervical\ncarcinoma, we performed a gene expression study on cases selected according to\nviral and clinical parameters. Using Coupled Two-Way Clustering and Sorting\nPoints Into Neighbourhoods methods, we identified a Cervical Cancer\nProliferation Cluster composed of 163 highly correlated transcripts, many of\nwhich corresponded to E2F pathway genes controlling cell proliferation, whereas\nno primary TP53 targets were present in this cluster. The average expression\nlevel of the genes of this cluster was higher in tumours with an early relapse\nthan in tumours with a favourable course (P=0.026). Moreover, we found that\nE6/E7 mRNA expression level was positively correlated with the expression level\nof the cluster genes and with viral DNA load. These findings suggest that HPV\nE6/E7 expression level plays a key role in the progression of invasive\ncarcinoma of the uterine cervix via the deregulation of cellular genes\ncontrolling tumour cell proliferation. HPV expression level may thus correspond\nto a biological marker useful for prognosis assessment and specific therapy of\nthe disease.",
"arxiv_id": "q-bio/0511019",
"authors": [
"Christophe Rosty",
"Michal Sheffer",
"Dafna Tsafrir",
"Nicolas Stransky",
"Ilan Tsafrir",
"Martine Peter",
"Patricia de Cremoux",
"Anne de La Rochefordiere",
"Remy Salmon",
"Thierry Dorval",
"Jean Paul Thiery",
"Jerome Couturier",
"Francois Radvanyi",
"Eytan Domany",
"Xavier Sastre-Garau"
],
"categories": [
"q-bio.TO",
"q-bio.QM"
],
"journal_ref": "Oncogene vol 24, p 7094-7104 (2005)",
"title": "Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma",
"url": "https://arxiv.org/abs/q-bio/0511019"
},
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