Institut Curie

The web supplement to
Peter M et al. 2010


Frequent Genomic Structural Alterations at HPV Insertion Sites in Cervical Carcinoma
Peter M1, Stransky N2, Couturier J3, Hupé P2,4,5,6, Barillot E4,5,6, Cottu P7, Radvanyi F2 and Sastre-Garau X1*

1Departments of Tumour Biology, 3Genetics,4Biostatistics, 7Medical Oncology, on behalf of the Gynaecological Oncology Group, Institut Curie, F-75248 Paris; 2CNRS UMR144, F-75248 Paris; 5INSERM, U900, F-75248 Paris;6Mines ParisTech, F-77300 Fontainebleau.7


To investigate whether integration of HPV DNA in cervical carcinoma is responsible for structural alterations of the host genome at the insertion site, a series of 34 primary cervical carcinoma and 8 cervical cancer-derived cell lines were analyzed. DNA copy number profiles were assessed using the Affymetrix GeneChip Human Mapping 250k sty array. HPV 16, 18 or 45 integration sites were determined using the DIPS-PCR technique. The genome status at integration sites was classified as follows: no change; amplification; transition normal/gain, normal/loss or gain/LOH. A single HPV integration site was found in 34 cases, two sites in 7 cases and 3 sites in one case (51 sites). Comparison between integration and DNA copy number profiles showed that the genome status was altered at 17/51 (33%) integration sites, corresponding to 16/42 cases (38%). Alterations detected were amplification in 9 cases, transition normal/loss in 4 cases, normal/gain in 3 cases and gain/LOH in one case. A highly significant association was found between genomic rearrangement and integration of HPV DNA (p<10-10). Activation of the replication origin located in viral integrated sequences in a cell line derived from one of the present cases of primary cervical carcinoma induced an increase of the amplification level of both viral and cellular DNA sequences flanking the integration locus. This mechanism may be implicated in the triggering of cell genomic structural alteration in carcinoma cells. Integration of HPV DNA frequently leads to structural alteration of the host genome and is likely to play a role in tumorigenesis.

Download data:
Oligos nucleotide sequences (.xls) Get it
Annotations (.xls) Get it
Affymetrix raw files (.CEL) Get them (.zip)
Affymetrix raw files (.csv) Get them (.zip)

Last modified January 29 2010 12:24:57