Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and are molecularly characterized by RAS pathway activation. Using exome and whole genome sequencing, we identified recurrent mutations in the protein translational regulator and in, and RAS pathway mutations were mutually exclusive; however, we found significant co-occurrence of mutations in and Missense mutations were clustered at the N-terminus of the protein in a region associated with its role in ensuring translational initiation fidelity. Coexpression of mutant and proteins promoted proliferation and clonogenic survival in LGSC cells, providing the first example of co-occurring, growth-promoting mutational events in ovarian cancer. .

The prevalence of infection with H. pylori in Australia was lower than rates reported in other developed countries, at 15.4%. This study provides important baseline measurements for future preventive measures including vaccine research and development. Further studies to determine subgroups at higher risk of infection may help target the more susceptible populations.

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Low-grade serous ovarian cancer (LGSC) is a morphologically and molecularly distinct subtype of ovarian cancer, accounting for ~10% of serous carcinomas. Women typically present at a younger age and have a protracted clinical course compared with the more common, high-grade serous ovarian cancer. Currently, primary treatment of LGSC is the same as other epithelial ovarian cancer subtypes, with treatment for most patients comprised of debulking surgery and platinum/taxane chemotherapy. Primary surgical cytoreduction to no visible residual disease remains a key prognostic factor, however the use of platinum-based chemotherapy in both the upfront and relapsed setting, is being questioned due to low response rates in LGSC. Most LGSC express steroid hormone receptors and selected patients may benefit from endocrine maintenance therapy following chemotherapy, in particular those with evidence of residual disease at completion of surgery. In the recurrent setting, while hormonal therapies may offer disease stabilization with relatively low toxicity, objective response rates remain low. Strategies to increase response rates, including combining with CDK4/6 inhibitors, are being investigated. LGSC have a high prevalence of activating somatic mutations in mitogen-activated protein kinase pathway genes, most commonly in KRAS, BRAF and NRAS. Trametinib, a MEK inhibitor, has shown efficacy over chemotherapy and endocrine therapy. The use of combination targeted therapies, immunotherapy and anti-angiogenic agents, remain active areas of investigation for the treatment of LGSC.