Systematic name M15664
Brief description The 'Cervical Cancer Proliferation Cluster' (CCPC): genes whose expression in cervical carcinoma positively correlates with that of the HPV E6 and E7 oncogenes; they are also differentially expressed according to disease outcome.
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16007141   Authors: Rosty C,Sheffer M,Tsafrir D,Stransky N,Tsafrir I,Peter M,de Crémoux P,de La Rochefordière A,Salmon R,Dorval T,Thiery JP,Couturier J,Radvanyi F,Domany E,Sastre-Garau X
Exact source Table 3S
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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Version history 3.0: First introduced

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