| 1. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 2. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 3. |
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| 4. |
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| 5. |
- Lao, O., et al.
(författare)
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Correlation between Genetic and Geographic Structure in Europe
- 2008
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 18:16, s. 1241-1248
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic structure of the European population is important, not only from a historical perspective, but also for the appropriate design and interpretation of genetic epidemiological studies. Previous population genetic analyses with autosomal markers in Europe either had a wide geographic but narrow genomic coverage [1, 2], or vice versa [3-6]. We therefore investigated Affymetrix GeneChip 500K genotype data from 2,514 individuals belonging to 23 different subpopulations, widely spread over Europe. Although we found only a low level of genetic differentiation between subpopulations, the existing differences were characterized by a strong continent-wide correlation between geographic and genetic distance. Furthermore, mean heterozygosity was larger, and mean linkage disequilibrium smaller, in southern as compared to northern Europe. Both parameters clearly showed a clinal distribution that provided evidence for a spatial continuity of genetic diversity in Europe. Our comprehensive genetic data are thus compatible with expectations based upon European population history, including the hypotheses of a south-north expansion and/or a larger effective population size in southern than in northern Europe. By including the widely used CEPH from Utah (CEU) samples into our analysis, we could show that these individuals represent northern and western Europeans reasonably well, thereby confirming their assumed regional ancestry. © 2008 Elsevier Ltd. All rights reserved.
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| 6. |
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| 7. |
- Bak-Misiuk, J., et al.
(författare)
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Creation of MnAs nanoclusters during processing of GaMnAs
- 2009
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Ingår i: Radiation Physics And Chemistry. - : Elsevier BV. - 0969-806X. ; 78, s. 116-119
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Konferensbidrag (refereegranskat)abstract
- GaMnAs layers on (0 0 1)-oriented GaAs substrates were grown by the molecular beam epitaxy (MBE) method. Structural properties of samples processed at up to 920 K under hydrostatic Ar pressure up to 1.1 GPa were investigated by X-ray, secondary ion mass spectroscopy and atomic force microscopy methods. The sign of strain (compressive or tensile) of the GaMnAs layers, related to a creation of MnAs nanoclusters, is found to be dependent on processing conditions and on primary structure defects, whereas it was independent of Mn concentration. An influence of the defects structure in as-grown samples on the strain state of processed GaMnAs layers is discussed. (C) 2009 Elsevier Ltd. All rights reserved.
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| 8. |
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| 9. |
- Bak-Misiuk, J., et al.
(författare)
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Pressure Variation of the Strain State of MnAs Nanoclusters Embedded in GaAs
- 2012
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Ingår i: Acta Physica Polonica. Series A: General Physics, Physics of Condensed Matter, Optics and Quantum Electronics, Atomic and Molecular Physics, Applied Physics. - 0587-4246. ; 121:4, s. 903-905
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Tidskriftsartikel (refereegranskat)abstract
- Granular GaAs:(Mn,Ga)As films were prepared by annealing at 500 degrees C under ambient and enhanced hydrostatic pressure (1.1 GPa), of Ga1-xMnxAs/GaAs layers (x = 0.025, 0.03, 0.04, 0.05 and 0.063) grown at 230 degrees C by molecular beam epitaxy method. Distinct influence of enhanced hydrostatic pressure applied during sample annealing on strain state of inclusions was found. An increase of lattice distortion and of strain of inclusions for the samples treated under hydrostatic pressure is related to different bulk moduli of GaAs and of MnAs
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| 10. |
- Bak-Misiuk, J., et al.
(författare)
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Variation of strain in granular GaAs:MnAs layers
- 2013
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Ingår i: Crystallography Reports. - 1063-7745. ; 58:7, s. 998-1001
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Tidskriftsartikel (refereegranskat)abstract
- Granular GaAs(MnAs) layers with different Mn concentration and various layer thickness were grown by MBE method and subjected to annealing at 500A degrees C under ambient and enhanced hydrostatic pressure. Distinct influence of hydrostatic pressure applied during annealing on strain state of layers as well as on hexagonal MnAs inclusions was found. Pressure induced strain of inclusions is related to different bulk moduli of GaAs and of hexagonal MnAs. Formation of hexagonal inclusions depends on concentration of Mn in interstitial position in as-grown samples.
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| 11. |
- Dynowska, E., et al.
(författare)
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Structural and magnetic properties of GaSb:MnSb granular layers
- 2011
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Ingår i: Radiation Physics and Chemistry. - : Elsevier BV. - 0969-806X. ; 80:10, s. 1051-1057
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Konferensbidrag (refereegranskat)abstract
- The results of structural and magnetic characterization of GaMnSb layers grown on GaSb(0 0 1) and GaAs(1 1 1) substrates are presented. The presence of hexagonal, highly oriented MnSb inclusions embedded in GaSb matrix has been demonstrated. The lattice parameters of these inclusions were the same as those for bulk MnSb for the layers grown on GaSb(1 0 0) substrate while for the layers grown on GaAs(1 1 1) the MnSb inclusions were strained. The influence of a presence of MnSb clusters on the lattice parameter of GaSb matrix has been demonstrated. It was confirmed that in all cases the MnSb clusters exhibit a ferromagnetic: behavior at room temperature. (C) 2011 Elsevier Ltd. All rights reserved.
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| 12. |
- Parsons, Michael T, et al.
(författare)
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Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants : An ENIGMA resource to support clinical variant classification
- 2019
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; , s. 1557-1578
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Tidskriftsartikel (refereegranskat)abstract
- The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.
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| 13. |
- Romanowski, P., et al.
(författare)
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Defect Structure of High-Temperature-Grown GaMnSb/GaSb
- 2010
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Ingår i: Acta Physica Polonica A. - 0587-4246. ; 117:2, s. 341-343
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Konferensbidrag (refereegranskat)abstract
- GaMnSb/GaSb(100) layers with embedded MnSb inclusions have been grown at 720 K using MBE technique. This paper presents the investigation of the defect structure of Ga1-xMnxSb layers with different content of manganese (up to x = 0.07). X-ray diffraction method using conventional and synchrotron radiation was applied. Dimensions and shapes of inclusions were detected by scanning electron microscopy. Depth profiles of elements were measured using secondary ion mass spectroscopy technique.
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