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Endogenous Proviruses
Published in Pimentel Enrique, Oncogenes, 2020
Another human endogenous virus, ERV3, consists also of a single copy and is located on chromosome 7.21 Monosomy or partial deletion of human chromosome 7 is frequently observed in ANLL. The proto-oncogene c-erb-B is located on the same chromosome but at a position (7p 11-13) outside the usual site of breakage in ANLL (7q32-34). It remains to be determined whether ERV3 is located near this chromosomal breakpoint and whether it plays a role in the fragility of this site.22 Although ERV3 retains the typical full-length gene order of retroviruses (5′LTR-gag-pol-env-3′LTR), it is apparently also a defective provirus due to the presence of terminator codons in the open reading frames of both its gag and pol gene sequences. ERV3 cannot function as an infectious virus but some of its genes may be capable of expression. The 5′ and 3′ LTRs of ERV3 resemble those of functional mammalian type-C retroviruses but have diverged from one another by 8.8%.22
Correlation and prognostic impact of human papilloma virus and p16-expression in advanced hypopharynx and larynx cancer treated with definitive radiotherapy
Published in Acta Oncologica, 2021
Pernille Lassen, Marie Schou, Jens Overgaard, Jan Alsner
By use of the DAHANCA-database, we identified patients with stage III-IV larynx and hypopharynx cancer treated with definitive radiotherapy according to DAHANCA guidelines between 1986 and 2006. Pre-treatment tumour blocks were evaluated by immunohistochemistry for p16-expression and classified as positive in case of strong cytoplasmatic and nuclear staining in >70% of tumour cells and in consideration of the typical microscopic appearance of an HPV-related tumour [15] (Figure 1). HPV DNA and RNA was analysed by qPCR using specific primer sets for HPV16 E6 and E7 and HPV18 E6 and E7. Internal reference genes were ERV3-1 and HBB for DNA and ACTR3, NDFIP1, and RPL37A for RNA. Overall survival was estimated by the Kaplan–Meier product-limit analysis and hazard ratio (HR) was estimated using Cox proportional hazards models.
Take three, test one: a cross-sectional study to evaluate the molecular detection of Chlamydia trachomatis and Neisseria gonorrhoeae in pooled pharyngeal, anorectal and urine samples versus single-site testing among men who have sex with men in Belgium
Published in Acta Clinica Belgica, 2020
Irith De Baetselier, Kara Krista Osbak, Hilde Smet, Chris Richard Kenyon, Tania Crucitti
In the SS protocol, four anorectal, one pharyngeal and no urine samples tested positive for NG (Table 1). All of these samples were detected using PS and US analyses. An additional three NG-positive anorectal samples were detected using PS and US testing. Two of them were initially positive in the SS testing by Abbott, but could not be confirmed. One of the anorectal samples was collected from a participant taking amoxicillin treatment for pharyngitis. ERV-3 qPCR testing performed on the SS related to the third PS positive case revealed a low amount of human material (25 cells/PCR vs. 8123 cells/PCR). Further, of the three anorectal SSs-containing inhibitors, two were reported as negative with the PS testing. One pharyngeal sample was negative in the SS testing but was weakly positive in the PS testing (DC = 0.89), however the NG could not be confirmed by the in-house RT-PCR. The contrary was observed for another pharyngeal sample, which was weakly positive in the SS testing (DC = 0.18) but was not further confirmed and which tested negative in the PS testing. There was no statistically significant difference in the positivity rates of NG as determined by SS (4.3%) or PS (6.8%) testing.
Genomic and immunologic correlates of LAG-3 expression in cancer
Published in OncoImmunology, 2020
Anshuman Panda, Jeffrey A. Rosenfeld, Eric A. Singer, Gyan Bhanot, Shridar Ganesan
The expression of normally silenced endogenous retroviral RNAs has been shown to be a potential mechanism of activation of innate immune signaling.23 We recently showed that expression of the potentially immunogenic endogenous retrovirus ERV3-2 is correlated with overall immune infiltration in 14 solid cancer types.24 To determine whether ERV expression is associated with LAG-3 expression, we tested for correlation between ERV3-2 expression and LAG-3 expression in these 14 cancer types. In 11 of the 14 cancer types, ERV3-2 expression was significantly (P < .05) correlated with LAG-3 expression (Figure 3(e)), suggesting that ERV3-2 expression may be a predictor of response to LAG-3 blockade in these cancer types. In addition to LAG-3, ERV3-2 expression was also associated with the upregulation of PD-1 and CTLA-4 pathways in most of these cancer types,24 suggesting the coordinated upregulation of multiple immune checkpoint genes in ERV-expressing tumors. In contrast, ERV3-2 expression was associated with overexpression of other checkpoint genes in a more cancer type-specific manner, such as the BTLA-HVEM pathway in only six cancer types and the TIM3-GAL9 pathway in only five cancer types (Figure 3(f)). A pan-cancer analysis to identify ERVs whose expressions correlated (Spearman Rho > 0, P < .05) or anti-correlated (Spearman Rho < 0, P < .05) with LAG-3 expression showed that ERV3-2 expression is correlated with LAG-3 expression in more cancer types than any other ERV (Supplementary Figure 5). Association between ERV3-2 expression and response to LAG-3 blockade with or without PD-1 blockade in these cancer types should be investigated in clinical trials.