Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

The water catchment : fast forward to the past

The Water Catchment: fast forward to the past comprises two parts: a creative piece and an exegesis. The methodology is Creative Practice as Research; a process of critical reflection, where I observe how researching the exegesis, in my case analysing how the social reality of an era in which an author writes affects their writing of the protagonist's journey, and how this in turn shapes how I write the hero's pathway in the creative piece. The genre in which the protagonist's journey is charted and represented is dystopian young adult fiction; hence my creative piece, The Water Catchment, is a novel manuscript for a dystopian young adult fantasy. It is a speculative novel set in a possible future and poses (and answers) the question: What might happen if water becomes the most powerful commodity on earth? There are two communities, called 'worlds' to create a barrier and difference where physical ones are not in evidence. A battle ensues over unfair conditions and access to water. In the end the protagonist, Caitlyn, takes over leadership heralding a new era of co-operation and water management between the two worlds. The exegesis examines how the hero's pathway, the journey towards knowledge and resolution, is best explored in young adult literature through dystopian narratives. I explore how the dystopian worlds of Ursula Le Guin's first and last books of The Earthsea Quartet are foundational, and lay this examination over an analysis of both the hero's pathway within and the social contexts outside of the novels. Dystopian narratives constitute a liberating space for the adolescent protagonist between the reliance on adults in childhood and the world of adults. In young adult literature such narratives provide fertile ground to explore those aspects informing an adolescent's future.