Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome.</p> <p>Methods</p> <p>Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified.</p> <p>Results</p> <p>The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function.</p> <p>Conclusions</p> <p>The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.</p

Does tumour biology determine surgical success in the treatment of epithelial ovarian cancer? A systematic literature review

BACKGROUND: Ovarian cancer is the most lethal gynaecological cancer. Progression-free and overall survival is significantly related to surgical success and residual disease volume. It is unclear whether this survival advantage is due to an intrinsic biological element of the tumour cells which enables successful surgery and improved prognosis, or alternatively the number of tumour sustaining cells remaining irrespective of differences in biology. METHODS: A systematic review of the literature was performed identifying studies that have investigated the association between biomarkers and surgical outcomes. We attempted validation of these results using The Cancer Genome Atlas ovarian cancer data sets. RESULTS: Thirty studies were identified of which sixteen determined protein expression, eight gene expression and one DNA methylation in association with surgical debulking. Individualised linear models adjusting for batch, stage and age identified only expression of the genes MTDH and insulin-like growth factor-1 receptor (IGF1R) to be significantly associated with debulking surgery (P<0.05, false discovery rate (FDR)<5%), although in the case of IGF1R this was in the opposite direction to previous findings. CONCLUSION: The majority of studies are limited by design, include heterogeneous samples and lack adjustment for major confounding factors. High quality detailed clinical annotations should be routinely collected in future to more accurately evaluate biomarkers of surgical outcome

Going to extremes: A metagenomic journey into the dark matter of life

The Virus-X—Viral Metagenomics for Innovation Value—project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of lif

Microbial communities in the subglacial waters of the Vatnajokull ice cap, Iceland

Subglacial lakes beneath the Vatnajokull ice cap in Iceland host endemic communities of microorganisms adapted to cold, dark and nutrient-poor waters, but the mechanisms by which these microbes disseminate under the ice and colonize these lakes are unknown. We present new data on this subglacial microbiome generated from samples of two subglacial lakes, a subglacial flood and a lake that was formerly subglacial but now partly exposed to the atmosphere. These data include parallel 16S rRNA gene amplicon libraries constructed using novel primers that span the v3-v5 and v4-v6 hypervariable regions. Archaea were not detected in either subglacial lake, and the communities are dominated by only five bacterial taxa. Our paired libraries are highly concordant for the most abundant taxa, but estimates of diversity (abundance-based coverage estimator) in the v4-v6 libraries are 3-8 times higher than in corresponding v3-v5 libraries. The dominant taxa are closely related to cultivated anaerobes and microaerobes, and may occupy unique metabolic niches in a chemoautolithotrophic ecosystem. The populations of the major taxa in the subglacial lakes are indistinguishable (>99% sequence identity), despite separation by 6 km and an ice divide; one taxon is ubiquitous in our Vatnajokull samples. We propose that the glacial bed is connected through an aquifer in the underlying permeable basalt, and these subglacial lakes are colonized from a deeper, subterranean microbiome. The ISME Journal (2013) 7, 427-437; doi:10.1038/ismej.2012.97; published online 13 September 201