Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
In PNAS this week, an international team led by investigators at the Indiana University School of Medicine points to the possibility of curbing metastatic ovarian cancer growth in BRCA1 mutation carriers by targeting the progesterone signaling pathway. Using immunohistochemistry, RNA sequencing, pathway analyses, and other approaches, the researchers saw signs that ovarian progesterone may help push high-grade serous carcinoma toward metastatic forms of the disease in mouse models. On the other hand, they found that ovarian cancer development and progression were dampened down in mice missing the progesterone receptor or in animals treated with a progesterone signaling inhibitor. From these and other results, the authors suggest that "targeting progesterone signaling represents a potentially effective non-surgical prophylactic strategy for prevention of ovarian cancer — and, by extension, breast cancer — in BRCA1-mutation carriers."
Johns Hopkins University School of Medicine researchers report In a paper slated to appear in PNAS this week on somatic LINE-1 (L1) retrotransposition events in adenocarcinoma tumors arising from a handful of tissue types. The team relied on single-cell amplification, L1-focused PCR, and targeted sequencing to assess somatic L1 insertion patterns in samples from 10 adenocarcinoma tumors occurring in the colon, pancreas, or stomach. Although the somatic retrotransposon insertion patterns varied from one sample to the next within each tumor type, the authors note that just a fraction of the L1 insertion events turned up in corresponding normal tissue types. "Our data indicate that the majority of somatic L1 insertions (83 percent) occur only after tumorigenesis is well underway. However, a significant percentage (17 percent) of these insertions were found both in the normal and tumor cells of [gastrointestinal] cancer patients," they wrote, noting that "[s]uch insertions could potentially initiate or drive tumorigenesis if they are present sufficiently early in the process to create driver mutations."
A team from the University of Notre Dame, the University of Witwatersrand, and elsewhere investigates introgression events and their effects on evolution, species radiation, and diversification in Anopheles mosquito species known for carrying malaria-causing parasites. With the help of new and available whole-genome sequencing, de novo assembly, and genome resequencing data, the researchers did population genomic and phylogenomic analyses to retrace introgression events in several An. funestus complex (AFC) mosquito species in Africa, including the malaria vector An. funestus sensu stricto. "We show that extensive inter-specific gene flow involving multiple species pairs has shaped the evolutionary history of the AFC since its diversification," they report, adding that these and other results hint that "introgression may be a common mechanism facilitating adaptation to new environments and enhancing vectorial capacity in Anopheles mosquitoes."