11. 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, original scientific article Abstract: 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. Keywords: BAP1, breast cancer, hereditary cancer syndromes, immunotherapy Published in DiRROS: 19.09.2022; Views: 618; Downloads: 249 Full text (1,12 MB) |
12. 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, original scientific article Abstract: 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. Keywords: hereditary cancer, RNA sequencing, spliceogenic Published in DiRROS: 07.09.2022; Views: 671; Downloads: 337 Full text (778,18 KB) This document has many files! More... |
13. 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, original scientific article Abstract: 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. Keywords: BRCA, ovarian cancer, tumor genotyping, HBOC Published in DiRROS: 06.09.2022; Views: 711; Downloads: 362 Full text (2,35 MB) This document has many files! More... |
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15. Priporočila za obravnavo bolnikov z rakom debelega črevesa in danke2020, dictionary, encyclopaedia, lexicon, manual, atlas, map Keywords: rak debelega črevesa, rak danke, bolniki, zdravljenje Published in DiRROS: 18.03.2022; Views: 1040; Downloads: 560 Full text (1,30 MB) This document has many files! More... |
16. Priporočila diagnostike in zdravljenja raka dojkAna Blatnik, Andraž Perhavec, Barbara Gazić, Barbara Vidergar-Kralj, Erika Matos, Ivica Ratoša, Janez Žgajnar, Kristijana Hertl, Marko Hočevar, Mateja Krajc, Nikola Bešić, Simona Borštnar, Marija Snežna Paulin-Košir, Tanja Marinko, Ulrika Klopčič, 2021, not set Keywords: presejanje, asimptomatske bolnice, simptomatske bolnice, genetsko svetovanje, slikovna diagnostika, citopatologija, kirurško zdravljenje, sistemsko zdravljenje, algoritmi, radioterapija, elektronske knjige Published in DiRROS: 17.03.2022; Views: 1025; Downloads: 605 Full text (2,03 MB) This document has many files! More... |
17. Klinična pot obravnave pacienta v Ambulanti za onkološko genetsko svetovanje in testiranjeMateja Krajc, Ana Blatnik, Tina Kerševan, Simona Hotujec, 2020, dictionary, encyclopaedia, lexicon, manual, atlas, map Keywords: genetika, rak prostate, genetsko testiranje, klinične poti Published in DiRROS: 16.03.2022; Views: 878; Downloads: 285 Full text (345,65 KB) |
18. Prednostno genetsko testiranje na zarodne mutacije pri bolnikih z metastatskim rakom prostate/pankreasa/dojk, ki potrebujejo izvid za zdravljenje raka s PARP inhibitorjiKsenija Strojnik, Ana Blatnik, Marta Banjac, Simona Hotujec, Natalija Klopčič, Janja Ocvirk, Srdjan Novaković, Mateja Krajc, 2021, dictionary, encyclopaedia, lexicon, manual, atlas, map Keywords: genetika, rak prostate, genetsko testiranje, klinične poti Published in DiRROS: 16.03.2022; Views: 891; Downloads: 475 Full text (354,42 KB) This document has many files! More... |
19. Klinična pot genetske obravnave bolnic z epitelijskim nemucinoznim rakom jajčnikov/jajcevodov/primarnim peritonealnim seroznim karcinomomErik Škof, Ksenija Strojnik, Marta Banjac, Ana Blatnik, Vida Stegel, Natalija Klopčič, Simona Hotujec, Srdjan Novaković, Mateja Krajc, 2021, dictionary, encyclopaedia, lexicon, manual, atlas, map Keywords: rak jajčnikov, genetika, zdravljenje, klinične poti Published in DiRROS: 16.03.2022; Views: 874; Downloads: 450 Full text (363,49 KB) This document has many files! More... |
20. Kaj je dedni rak? : dedno pogojeni raki - genetsko svetovanje in testiranjeAna Blatnik, Mateja Krajc, Ksenija Strojnik, Srdjan Novaković, Barbara Perić, Marta Banjac, Janez Žgajnar, 2020, not set Keywords: medicinska genetika, genetsko testiranje Published in DiRROS: 11.03.2022; Views: 975; Downloads: 297 Full text (1,43 MB) |