Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Crustal recycling by subduction erosion in the central Mexican Volcanic Belt

Recycling of upper plate crust in subduction zones, or ‘subduction erosion’, is a major mechanism of crustal destruction at convergent margins. However, assessing the impact of eroded crust on arc magmas is difficult owing to the compositional similarity between the eroded crust, trench sediment and arc crustal basement that may all contribute to arc magma formation. Here we compare Sr–Nd–Pb–Hf and trace element data of crustal input material to Sr–Nd–Pb–Hf–He–O isotope chemistry of a well-characterized series of olivine-phyric, high-Mg# basalts to dacites in the central Mexican Volcanic Belt (MVB). Basaltic to andesitic magmas crystallize high-Ni olivines that have high mantle-like 3He/4He = 7–8 Ra and high crustal δ18Omelt = +6.3–8.5‰ implying their host magmas to be near-primary melts from a mantle infiltrated by slab-derived crustal components. Remarkably, their Hf–Nd isotope and Nd/Hf trace element systematics rule out the trench sediment as the recycled crust end member, and imply that the coastal and offshore granodiorites are the dominant recycled crust component. Sr–Nd–Pb–Hf isotope modeling shows that the granodiorites control the highly to moderately incompatible elements in the calc-alkaline arc magmas, together with lesser additions of Pb- and Sr-rich fluids from subducted mid-oceanic ridge basalt (MORB)-type altered oceanic crust (AOC). Nd–Hf mass balance suggests that the granodiorite exceeds the flux of the trench sediment by at least 9–10 times, corresponding to a flux of ⩾79–88 km3/km/Myr into the subduction zone. At an estimated thickness of 1500–1700 m, the granodiorite may buoyantly rise as bulk ‘slab diapirs’ into the mantle melt region and impose its trace element signature (e.g., Th/La, Nb/Ta) on the prevalent calc-alkaline arc magmas. Deep slab melting and local recycling of other slab components such as oceanic seamounts further diversify the MVB magmas by producing rare, strongly fractionated high-La magmas and a minor population of high-Nb magmas, respectively. Overall, the central MVB magmas inherit their striking geochemical diversity principally from the slab, thus emphasizing the importance of continental crust recycling in modern solid Earth relative to its new formation in modern subduction zones

Koncert Gudačkog komornog orkestra Muzičke akademije (Gudački komorni orkestar i solistica Tonka Philips (viola), 9. 3. 2023.)

Drugi dio snimke koncerta održanog na Muzičkoj akademiji u Koncertnoj dvorani "Blagoje Bersa" 9. 3. 2023. Izvođači: Gudački komorni orkestar Muzičke akademije Sveučilišta u Zagrebu, solistica Tonka Philips (viola). Umjetničko vodstvo: red. prof. art. Anđelko Krpan. Program: 1. Georg Friedrich Händel: Concerto grosso u d-molu, op. 6, br. 10 (Ouverture / Allegro – Lentement – Allegro – Allegro – Allegro moderato); 2. Johann Georg Benda: Grave za violu i gudače; 3. Milko Kelemen: Koncertantne improvizacije (Allegretto – Andante sostenuto / Allegro giusto – Moderato assai – Comodo – Allegro scherzando – Molto vivace, quasi presto); 4. Dmitrij Šostakovič: Simfonija za gudače u As-duru, 118a (Andante – Allegretto furioso – Adagio – Allegretto)