RESUMO
In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built and analyzed a database comprised of 1455 cases, including HPV genotypes and tumor localizations. Host DNA sequences targeted by viral integration were classified as "non-recurrent" (one single reported case; 838 loci), "weakly recurrent" (two reported cases; 82 loci), and highly recurrent (≥3 cases; 43 loci). Whereas the overall rate of cancer-related target genes was 3.3% in the Gencode database, this rate increased to 6.5% in "non-recurrent", 11.4% in "weakly recurrent", and 40.1% in "highly recurrent" genes targeted by integration (p = 4.9 × 10-4). This rate was also significantly higher in tumors associated with high-risk HPV16/18/45 than other genotypes. Among the genes targeted by HPV insertion, 30.2% corresponded to direct or indirect druggable targets, a rate rising to 50% in "highly recurrent" targets. Using data from the literature and the DepMap 23Q4 release database, we found that genes targeted by viral insertion could be new candidates potentially involved in HPV-associated oncogenesis. A more systematic characterization of HPV/host fusion DNA sequences in HPV-associated cancers should provide a better knowledge of HPV-driven carcinogenesis and favor the development of personalize patient treatments.
RESUMO
We report the reproductive strategy of the nematode Mesorhabditis belari This species produces only 9% males, whose sperm is necessary to fertilize and activate the eggs. However, most of the fertilized eggs develop without using the sperm DNA and produce female individuals. Only in 9% of eggs is the male DNA utilized, producing sons. We found that mixing of parental genomes only gives rise to males because the Y-bearing sperm of males are much more competent than the X-bearing sperm for penetrating the eggs. In this previously unrecognized strategy, asexual females produce few sexual males whose genes never reenter the female pool. Here, production of males is of interest only if sons are more likely to mate with their sisters. Using game theory, we show that in this context, the production of 9% males by M. belari females is an evolutionary stable strategy.
