Merkel Cell Carcinoma of the Skin: A New Type of Virus-Associated Human Tumour
X Sastre-Garau, M Peter, MF Avril, H Laude, J Couturier, F Rozenberg, A Almeida, F Boitier, A Carlotti, B Couturaud, N Dupin. Institut Curie, Paris, France; Groupe Hospitalier Cochin-St Vincent de Paul, Paris, France
Background: Merkel cell carcinoma (MCC), a skin tumour with neuro-endocrine features, was recently found to be associated with a new type of human polyomavirus, called Merkel Cell Virus (MCV). We investigated the specificity of this association as well as a causal role of MCV in oncogenesis.
Design: In this work, DNA and RNA from 10 cases of MCC were analysed using PCR and RT-PCR. DNA from 1241 specimens of a wide range of human tumours was also analysed. The DIPS technique was used to identify the integration locus of viral DNA sequences. Array-CGH was performed to analyse structural alterations of the cell genome.
Results: MCV DNA sequences were found in all 10 cases of MCC and in none of the 1241 specimens of other tumour types. Clonal integration of MCV into the host genome was seen in all MCC cases. A recurrent pattern of conserved viral sequences which encompassed the replication origin, the small tumour (ST) and the 5' part of the large tumour (LT) antigen DNA sequences was observed. Both ST and LT viral sequences were found to be significantly expressed in all MCC. Neither recurrent site of integration nor alteration of cellular genes located near the viral sequences were observed.
Conclusions: The tight association of MCV with MCC, the clonal pattern of MCV integration as well as the expression of the viral oncoproteins strongly support a causative role for MCV in the tumour process. This information will help the development of novel approaches for assessment and therapy of MCC and biologically related tumours.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 56, Wednesday Morning