LB12
Variable transcriptional activity of endogenous retroviruses in cutaneous T-Cell lymphomas
Pilvi Maliniemi1, Oliver Frank2, Sonja Hahtola1, Michelle Vincendeau3, Kirsi Niiranen1, Emilia Carlsson1, Leena Karenko1, Wolfgang Seifarth2, Christine Leib-Msch3, Annamari Ranki1
1Helsinki University Central Hospital, University of Helsinki, Finland; 2University of Heidelberg, Mannheim, Germany; 3Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Molecular Virology, Neuherberg, Germany
Background
Cutaneous T-cell lymphomas (CTCLs) is a group of heterogeneous non-Hodgkin
lymphomas with homing preference to skin. While CTCLs show a growing incidence,
the mechanisms leading to the disease are mostly elusive. We have shown that certain
chromosomal aberrations are associated with the progression of the disease.
Interestingly, CTCL patients show antibodies to some retroviral core and
anxillary proteins, but no replication-capable retroviruses have been found.
Furthermore, human endogenous retroviruses (HERVs), which are normal,
transposable components of human genome, may be overexpressed in cancers.
Generally they are active in human cells in a tissue-specific manner. Here we
initiated a study to explore the role of HERVs in relation to chromosomal
aberrations in CTCL pathogenesis.
Method
We used a retrovirus-specific microarray to identify the transcriptional
profile of HERV sequences in 12 CTCL and five psoriasis patients, both in
non-malignant and skin lesion samples. The results were confirmed with
quantitative RT-PCR. Moreover we searched for specific HML-6 and HERV-E
transcripts, in which the latter one has been proven to encode a tumour
antigen.
Results
The analysis of non-malignant samples revealed a distinct, skin-specific
HERV expression profile that consists of seven constitutively active HERV taxa.
For corresponding lesion samples, generally, relatively minor changes in HERV
transcription was observed. Only one (HERV-W) out of the seven showed clearly a
higher levels of HERV transcription. In various subsets of patients, however,
activation of some and increased activity of a few HERVs were detected. HML-6
showed the most obvious differences of expression activity between
non-malignant and lesion samples in microarray analysis.
Conclusion
This study revealed a characteristic HERV transcription pattern in human
skin. The data resembled with previous studies done with other tissues showing
that individual variability is a typical feature of HERV transcription. Further
studies based on CTCL-related alterations in HERV activity are ongoing.
