by Wildaisy Fl on Tuesday, April 26, 2011:
The Towers paper argued that because they found identical integration sites, XMRV/HGRV had to be contamination. However, this Selten 1986 paper shows that they identified independent integrations by a retrovirus at the same nucleotide position.
Here is the belief stated in Garson, Kellam and Towers:
With the exception of a single early publication on avian sarcoma-leukosis virus, which was refuted by later work , sequencing studies of thousands of retroviral integration sites have to our knowledge never identified exactly the same site twice. It therefore appears very unlikely that the sites illustrated in Figure 1 are the result of independent integrations into identical genomic locations in a prostate tumour in vivo and an experimentally infected cell line in vitro, on two separate occasions.
Selton et al 1986 therefore shows that Garson et al's "knowledge" was incomplete, as independent integrations by a retrovirus - in fact, an MLV - have been shown to occur at the same nucleotide position. Therefore the fact that they found identical integration sites does not in itself argue for contamination; the improbability argument they made has to be seen as weakened if not destroyed.
Integration in lymphomas 10 and 17 occurred about 140 nucleotides downstream of the pim-1 coding region at the same nucleotide position (Figures 3 and 4) whereas the provirus in lymphoma 34 was integrated 3 nucleotides further downstream from this latter site (Figures 3 and 4). This result shows that within this region integration is nonrandom.
You can see the integration sites in Fig. 4. Not only were the proviral insertions from tumors 10 and 17 at the same nucleotide, but the one for tumor 34 occured only 3 base pairs down. Two more (32 and 54) are only a few bp apart from one another as well (and aren't that far upstream of those other three).
Garson, Kellam and Towers (2011): http://www.mecfsforums.com/index.php/topic,6572.msg76501.html#msg76501
Towers et al, 2011, No XMRV in HIV patients in London. PLoS One, March 2011 | Volume 6 | Issue 3 | e18096
Selten 1986: primary structure of the putative oncogene pim-1: http://www.mecfsforums.com/index.php/topic,7002.new.html#new;
Shen-Ong, G. L., M. Potter, J. F. Mushinski, S. Lavu, and E. P.
Reddy. 1984. Activation of the c-myb locus by viral insertional
mutagenesis in plasmacytoid lymphosarcomas. Science
See full discussion here: http://www.mecfsforums.com/index.php/topic,6994.0.html