51. BAP1-defficient breast cancer in a patient with BAP1 cancer syndromeAna Blatnik, Domen Ribnikar, Vita Šetrajčič Dragoš, Srdjan Novaković, Vida Stegel, Biljana Grčar-Kuzmanov, Nina Boc, Barbara Perić, Petra Škerl, Gašper Klančar, Mateja Krajc, 2022, izvirni znanstveni članek Povzetek: BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions, BAP1 alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline BAP1 likely pathogenic variant (c.898_899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in BAP1 (partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer. Ključne besede: BAP1, breast cancer, hereditary cancer syndromes, immunotherapy Objavljeno v DiRROS: 19.09.2022; Ogledov: 446; Prenosov: 180 Celotno besedilo (1,12 MB) |
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53. Identification of spliceogenic variants beyond canonical GT-AG splice sites in hereditary cancer genesVita Šetrajčič Dragoš, Ksenija Strojnik, Gašper Klančar, Petra Škerl, Vida Stegel, Ana Blatnik, Marta Banjac, Mateja Krajc, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process. Twelve VUS that were predicted to cause splicing defects were selected for mRNA analysis. Here, we report a functional characterization of 12 variants located beyond the first two intronic nucleotides using RNAseq in APC, ATM, FH, LZTR1, MSH6, PALB2, RAD51C, and TP53 genes. Based on the analysis of mRNA, we have successfully reclassified 50% of investigated variants. 25% of variants were downgraded to likely benign, whereas 25% were upgraded to likely pathogenic leading to improved clinical management of the patient and the family members. Ključne besede: hereditary cancer, RNA sequencing, spliceogenic Objavljeno v DiRROS: 07.09.2022; Ogledov: 464; Prenosov: 238 Celotno besedilo (778,18 KB) Gradivo ima več datotek! Več... |
54. Real-world data on detection of germline and somatic pathogenic/likely pathogenic variants in BRCA1/2 and other susceptibility genes in ovarian cancer patients using next generation sequencingVida Stegel, Ana Blatnik, Erik Škof, Vita Šetrajčič Dragoš, Mateja Krajc, Brigita Gregorčič, Petra Škerl, Ksenija Strojnik, Gašper Klančar, Marta Banjac, Janez Žgajnar, Maja Ravnik-Oblak, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients. Ključne besede: BRCA, ovarian cancer, tumor genotyping, HBOC Objavljeno v DiRROS: 06.09.2022; Ogledov: 504; Prenosov: 274 Celotno besedilo (2,35 MB) Gradivo ima več datotek! Več... |
55. Availability and costs of medicines for the treatment of tuberculosis in EuropeGunar Günther, Lorenzo Guglielmetti, Claude Leu, Christoph Lange, Frank van Leth, 2022, pregledni znanstveni članek Povzetek: Objectives. To evaluate the access to comprehensive diagnostics and novel anti-tuberculosis medicines in European countries. Methods. We investigated access to genotypic and phenotypic M. tuberculosis drug susceptibility testing, availability of anti-tuberculosis drugs and calculated cost of drugs and treatment regimens at major tuberculosis treatment centers in countries of the World Health Organization (WHO) European region where rates of drug-resistant tuberculosis are highest among all WHO regions. Results are stratified by middle-income and high-income countries. Results. Overall, 43 treatment centers in 43 countries participated in the study. For WHO Group A drugs, the frequency of countries with availability of phenotypic drug susceptibility testing was as follows: 30/40 (75%) for levofloxacin, 33/40 (82%) for moxifloxacin, 19/40 (48%) for bedaquiline and 29/40 (72%) for linezolid, respectively. Overall, 36/43 (84%) and 24/43 (56%) of countries had access to bedaquiline and delamanid, while only 6/43 (14%) had access to rifapentine. Treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was only available in 17/43 (40%) of the countries. Median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for six months) and extensively drug-resistant tuberculosis (including bedaquiline, delamanid and a carbapenem) were € 44 (min-max € 15-152), € 764 (min-max € 542-15152) and € 8709 (min-max € 7965-11759) in middle-income countries (n=12), and € 280 (min-max-€78-1084), € 29765 (min-max 11116-40584), € 217591 (min-max € 82827-320146) in high-income countries (n=29). Conclusion. In countries of the WHO Europe Region there is a widespread lack of drug susceptibility testing capacity to new and re-purposed anti-tuberculosis drugs, lack of access to essential medications in several countries and high treatment cost for drug-resistant tuberculosis. Ključne besede: tuberculosis - drug therapy, Mycobacterium tuberculosis - drug therapy, health care costs - drug therapy, Europe Objavljeno v DiRROS: 31.08.2022; Ogledov: 693; Prenosov: 144 Povezava na datoteko |
56. Gospodarjenje s tujerodnimi drevesnimi vrstami v urbanem prostoru alpskega prostoraAjša Alagić, Aleksander Marinšek, Ana Dolenc, Andrey Krasovskiy, Anica Simčič, Anja M. Bindewald, Anja Müller-Meißner, Bénédicte Baxerres, Claudia Cocozza, Debojyoti Chakraborty, Janez Kermavnar, Lado Kutnar, Simon Zidar, Tina Trampuš, Živa Bobič Červek, 2022, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: tujerodne drevesne vrste, Alpe, invazivne drevesne vrste, gospodarjenje z gozdovi, podnebne spremembe, urbani prostor Objavljeno v DiRROS: 12.08.2022; Ogledov: 1133; Prenosov: 254 Celotno besedilo (4,27 MB) |
57. Handbook for non native tree species in the urban spaceAjša Alagić, Aleksander Marinšek, Ana Dolenc, Andrey Krasovskiy, Anica Simčič, Anja M. Bindewald, Anja Müller-Meißner, Bénédicte Baxerres, Claudia Cocozza, Debojyoti Chakraborty, Janez Kermavnar, Lado Kutnar, Simon Zidar, Tina Trampuš, Živa Bobič Červek, 2022, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: non-native tree species, Alps, invasive alien species, forest management, urbanspace, climate changes Objavljeno v DiRROS: 12.08.2022; Ogledov: 520; Prenosov: 197 Celotno besedilo (4,25 MB) |
58. Gospodarjenje s tujerodnimi drevesnimi vrstami v gozdovih alpskega prostoraSonia Abluton, Ajša Alagić, Bénédicte Baxerres, Frédéric Berger, Anja M. Bindewald, Sylvain Bouquet, Martin Braun, Giuseppe Brundu, Patricia Detry, Freya-Isabel Georges, Janez Kermavnar, Lado Kutnar, Aleksander Marinšek, Anica Simčič, Simon Zidar, 2022, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: tujerodne drevesne vrste, Alpe, invazivne drevesne vrste, gospodarjenje z gozdovi, podnebne spremembe Objavljeno v DiRROS: 12.08.2022; Ogledov: 1068; Prenosov: 234 Celotno besedilo (3,25 MB) |
59. Management of non-native tree species in forests of the Alpine spaceSonia Abluton, Ajša Alagić, Bénédicte Baxerres, Frédéric Berger, Anja M. Bindewald, Sylvain Bouquet, Martin Braun, Giuseppe Brundu, Patricia Detry, Freya-Isabel Georges, Janez Kermavnar, Lado Kutnar, Aleksander Marinšek, Anica Simčič, Simon Zidar, 2022, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: non-native tree species, Alps, invasive alien species, forest management, climate changes Objavljeno v DiRROS: 12.08.2022; Ogledov: 554; Prenosov: 184 Celotno besedilo (3,20 MB) |
60. Priročnik za prepoznavanje tujerodnih drevesnih vrst v alpskem prostoruAjša Alagić, Bénédicte Baxerres, Frédéric Berger, Anja M. Bindewald, Sylvain Bouquet, Giuseppe Brundu, Debojyoti Chakraborty, Patricia Detry, Freya-Isabel Georges, Quentin Guillory, Janez Kermavnar, Lado Kutnar, Katharina Lapin, Aleksander Marinšek, Eric Mermin, Anja Müller-Meißner, Janine Oettel, Anica Simčič, Simon Zidar, 2022, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: tujerodne drevesne vrste, Alpe, invazivne drevesne vrste Objavljeno v DiRROS: 12.08.2022; Ogledov: 1206; Prenosov: 389 Celotno besedilo (19,49 MB) |