Myklebost and Børresen-Dale co-authors on recent Science article on mobile DNA in cancer
Ola Myklebost from the Department of Tumor Biology and Anne-Lise Børresen-Dale co-author an article published in Science (journal impact factor 31) Aug 1st, entitled "Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes".
This article described the detailed analysis of rearrangements involving L1 retrotransposons in multiple cancer types, including breast and bone cancer, based on sub studies within the framework of the International Cancer genome Consortium. Børresen-Dale’s group is a partner in the Breast Cancer Consortium, and that of Ola Myklebost in the Bone Cancer Group.
These retrotransposons are molecular parasites, able to copy themselves and insert these copies into new positions in the genome. However, in normal cells, their promoters are usually inactivated by methylation, with the notable exception of neuronal progenitors, where retrotransposion is at least to some extent reacitvated during early brain development, leading to genome changes between subclones of brain cells. However, as the epigenome also is frequently destabilized in cancer, retrotransposition may be reactivated and contribute to genome instability.
The promoters of L1 elements were shown to be hypomethylated, and retrotransposition was shown to be particularly frequent in colorectal and lung cancer. Most strikingly, the process is imprecise, and may hijack parts of neighboring genes during excision. Thus fragements of genes are moved around in the genome, often by several cycles, and this may contribute both to oncogenic events, and to erronous scoring as translocations when tumours are sequenced by less prercise algoritms.
Links:
The article:
Science 1 August 2014:
Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes
Jose M. C. Tubio1 et al.
Vol. 345 no. 6196
The International Cancer Genome Consortium
Home page of Ola Myklebost' group - Molecular characterization of mesenchymal cancer development
Home page of Anne-Lise Børresen-Dale's group - Molecular Biology of Breast Cancer
Ola Myklebost's CV and publications