1. Uspešno genetsko testiranje 59 let starega vzorca tkiva : pomen arhivskih vzorcev pri opredeljevanju dednih predispozicij za razvoj rakaVita Šetrajčič Dragoš, Vida Stegel, Olga Blatnik, Mateja Krajc, Ana Blatnik, 2026, strokovni članek Povzetek: Predstavljamo uspešno genetsko analizo 59 let starega, arhivskega, v formalinu fiksiranega in v parafin vklopljenega (FFPE) vzorca tkiva z namenom opredelitve dedne predispozicije za razvoj raka. V družinah z obremenilno družinsko anamnezo raka, kjer ključni oboleli sorodniki niso več živi, je povednost standardnega genetskega testiranja živih družinskih članov pogosto omejena. V predstavljenem primeru je bila iz tumorskega vzorca, odvzetega leta 1960, izolirana DNA in izvedeno sekvenciranje naslednje generacije (NGS). Kljub starosti vzorca so bili doseženi vsi parametri kakovosti za zanesljivo molekularno-genetsko analizo. Ugotovljena je bila patogena različica CHEK2:c. 1100del p.(Thr367Metfs*15), povezana s povečano ogroženostjo za razvoj raka dojk. Družinsko testiranje je omogočilo natančnejšo opredelitev ogroženosti pri živih sorodnikih in ustreznejše preventivne usmeritve. Opisani primer poudarja klinično vrednost analize arhivskih FFPE vzorcev pri genetski obravnavi družin s sumom na dedno nagnjenost k raku ter odpira vprašanje pomena dolgoročne hrambe reprezentativnega histološkega materiala za diagnostične, preventivne in raziskovalne namene.
Ključne besede: arhivski histološki preparati, sekvenciranje naslednje generacije, genetsko testiranje, dedne predispozicije za razvoj raka
Objavljeno v DiRROS: 31.07.2026; Ogledov: 117; Prenosov: 37
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2. Two recurrent pathogenic/likely pathogenic variants in PALB2 account for half of PALB2 positive families in SloveniaVita Andreja Mesarič, Ana Blatnik, Kristina Drusany Starič, Ksenija Strojnik, Vida Stegel, Simona Hotujec, Vita Šetrajčič Dragoš, Petra Škerl, Srdjan Novaković, Mateja Krajc, 2024, izvirni znanstveni članek Ključne besede: breast and ovarian cancer syndrome, HBOC syndrome, multigene panel testing
Objavljeno v DiRROS: 09.06.2026; Ogledov: 203; Prenosov: 173
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3. Genetske analize arhivskih vzorcev tkiva pokojnikov z namenom ugotavljanja dednih vzrokov rakaAna Blatnik, Vita Šetrajčič Dragoš, Vida Stegel, Olga Blatnik, Ksenija Strojnik, Srdjan Novaković, Mateja Krajc, 2024, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: dedni rak, patologija, onkologija
Objavljeno v DiRROS: 25.02.2026; Ogledov: 460; Prenosov: 145
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4. Are there clinically relevant prognostic factors in diffuse large B-cell lymphoma beyond International Prognostic IndexMilica Miljković, Vita Šetrajčič Dragoš, Gorana Gašljević, Srdjan Novaković, Lučka Boltežar, Barbara Jezeršek Novaković, 2025, izvirni znanstveni članek Povzetek: Diffuse large B-cell lymphoma (DLBCL) has variable prognosis, with only 50 to 60% of patients cured by standard first line treatment. Identifying patients unlikely to benefit from standard first line therapy is therefore crucial. Schmitz’s study identified four molecular subtypes of DLBCL with differing prognoses: MCD, BN2, N1, and EZB, with BN2 and EZB showing more favorable outcomes. This study aimed to evaluate the effectiveness of the Archer FusionPlex Lymphoma Assay in identifying the newly defined genetic subtypes of DLBCL, while also exploring the association between immunohistochemical (IHC) and next-generation sequencing (NGS) methods for classifying the cell of origin (COO) and assessing their predictive value for patient survival. Materials and methods. We classified 131 DLBCL patients using Hans algorithm into GCB (germinal center B-celllike) and ABC (activated B-cell-like) subtypes, and with NGS applying Archer FusionPlex lymphoma assay into ABC, GCB, unclassified, and into Schmitz’s novel genetic subtypes. A mutational analysis of just 7 genes (MYD88L265P, CD79B, EZH2, NOTCH1, NOTCH2, BCL2, and BCL6) was used for genetic classification. Various statistical models were applied to assess survival differences between subtypes. Finally, STRATOS analysis was conducted to validate our preliminary statistical findings. Results. 35.9% of patients were successfully classified into new genetic subtypes, with acceptable consistency between IHC and NGS method for COO determination. However, the new genetic subtype classification by NGS did not correlate with overall survival, nor did the COO classifications by IHC or NGS. The inclusion of these classifications also did not improve the predictive value of models compared to the basic model based on the International Prognostic Index (IPI) only. Conclusions. The Archer FusionPlex Lymphoma assay showed a somewhat lower detection rate of novel genetic subtypes compared to reports based on exome sequencing, yet identified novel genetic subtypes in over one-third of patients. However, an in-depth STRATOS statistical analysis did not confirm its predictive value for DLBCL prognosis, likely due to factors like patient selection and sample size limitations.
Ključne besede: diffuse large B-cell lymphoma, new genetic types, prognostic factors
Objavljeno v DiRROS: 26.11.2025; Ogledov: 759; Prenosov: 214
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5. Male sex, B symptoms, bone marrow involvement, and genetic alterations as predictive factors in diffuse large B-cell lymphoma : Elektronski virMatej Panjan, Vita Šetrajčič Dragoš, Gorana Gašljević, Srdjan Novaković, Barbara Jezeršek Novaković, 2025, izvirni znanstveni članek Povzetek: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are not cured with first-line chemoimmunotherapy, resulting in poor prognosis. Schmitz et al. classified DLBCL into four prognostic genetic groups using whole-exome sequencing. We applied a simplified approach using a targeted next-generation sequencing assay (Archer FusionPlex Lymphoma Assay) to analyze samples from 105 patients—53 with a progression-free survival (PFS) < 2 years (the “Relapse group”) and 52 with a PFS > 5 years (the “Remission group”) following first-line systemic treatment. Patients were classified according to Schmitz et al. into the following categories: “MCD” (MYD88L265P and CD79B alteration), “N1” (NOTCH1 alteration), “BN2” (NOTCH2 alteration and BCL6 translocation), and “EZB” (EZH2 alteration and BCL2 translocation). The predictive value of this simplified genetic classification and of relevant clinical features were evaluated. The “Relapse group” included more patients classified as MCD and N1, while fewer were classified as EZB and BN2. Also, cell-of-origin (COO) characteristics and the size of N1 aligned with the classification of Schmitz et al. However, the limited sample size precludes definitive conclusions about the predictive value of our simplified approach. Additionally, male sex, B symptoms, and bone marrow involvement were associated with relapse. Therefore, these clinical features may be useful in predicting outcomes until an effective molecular classification is widely adopted.
Ključne besede: DLBCL, genetic classification, predictive, lymphoma
Objavljeno v DiRROS: 21.11.2025; Ogledov: 653; Prenosov: 262
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6. CD56-positive diffuse large B-cell lymphoma : comprehensive analysis of clinical, pathological, and molecular characteristics with literature reviewGorana Gašljević, Lučka Boltežar, Srdjan Novaković, Vita Šetrajčič Dragoš, Barbara Jezeršek Novaković, Veronika Kloboves-Prevodnik, 2023, izvirni znanstveni članek Povzetek: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. The expression of CD56 in DLBCL is highly unusual. Little is known about its incidence and clinical importance. So far, no genetic profiling was performed in CD56 positive DLBCL.Patients and methods. Tissue microarrays have been constructed, sectioned, and stained by H&E and immuno-histochemistry for 229 patients with DLBCL diagnosed 2008–2017. For CD56 positive cases, clinical data was collected including age at diagnosis, stage of the disease, International Prognostic Index (IPI) score, treatment scheme and number of chemotherapy cycles, radiation therapy, treatment outcome, and possible relapse of the disease. Overall survival (OS) and progression-free survival (PFS) were calculated. For four patients, RNA was extracted and targeted RNA (cDNA) sequencing of 125 genes was performed with the Archer FusionPlex Lymphoma kit.Results. CD56 expression was found in 7 cases (3%). The intensity of expression varied from weak to moderate focal, to very intensive and diffuse. All patients had de novo DLBCL. The median age at the time of diagnosis was 54.5 years. Five of them were women and 2 males. According to the Hans algorithm, 6 patients had the germinal centre B cells (GBC) type and one non-GBC (activated B-cell [ABC]) type, double expressor. Genetic profiling of four patients ac-cording to Schmitz’s classification showed that 1 case was of the BN2 subtype, 1 of EZB subtype, 2 were unclassified. The six treated patients reached a complete response and did not experience progression of the disease during the median follow-up period of 80.5 months.Conclusions. We report on one of the largest series of CD56+DLBCL with detailed clinicopathological data and for the first time described genetical findings in a limited number of patients. Our results show that CD56 expression is rare, but seems to be present in prognostic favourable subtypes of DLBCL not otherwise specified (NOS) as tested by immunohistochemical or genetic profiling
Ključne besede: diffuse large B-cell lymphoma, immunohistochemistry, lymphomas, CD56
Objavljeno v DiRROS: 25.07.2024; Ogledov: 1518; Prenosov: 525
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8. New approach for detection of normal alternative splicing events and aberrant spliceogenic transcripts with long-range PCR and deep RNA sequencingVita Šetrajčič Dragoš, Vida Stegel, Ana Blatnik, Gašper Klančar, Mateja Krajc, Srdjan Novaković, 2021, izvirni znanstveni članek Povzetek: RNA sequencing is a promising technique for detecting normal and aberrant RNA isoforms. Here, we present a new single-gene, straightforward 1-day hands-on protocol for detection of splicing alterations with deep RNA sequencing from blood. We have validated our method%s accuracy by detecting previously published normal splicing isoforms of STK11 gene. Additionally, the same technique was used to provide the first comprehensive catalogue of naturally occurring alternative splicing events of the NBN gene in blood. Furthermore, we demonstrate that our approach can be used for detection of splicing impairment caused by genetic variants. Therefore, we were able to reclassify three variants of uncertain significance: NBN:c.584G>A, STK11:c.863-5_863-3delCTC and STK11:c.615G>A. Due to the simplicity of our approach, it can be incorporated into any molecular diagnostics laboratory for determination of variant%s impact on splicing.
Ključne besede: RNA sequencing, DNA variant, splicing
Objavljeno v DiRROS: 21.09.2022; Ogledov: 2000; Prenosov: 1227
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9. Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransferUrška Kamenšek, Katja Uršič Valentinuzzi, Boštjan Markelc, Maja Čemažar, Vita Šetrajčič Dragoš, Gregor Serša, 2021, izvirni znanstveni članek Povzetek: In situ vaccination is a promising immunotherapeutic approach, where various local ablative therapies are used to induce an immune response against tumor antigens that are released from the therapy-killed tumor cells. We recently proposed using intratumoral gene electrotransfer for concomitant transfection of a cytotoxic cytokine tumor necrosis factor-% (TNF%) to induce in situ vaccination, and an immunostimulatory cytokine interleukin 12 (IL-12) to boost the primed immune response. Here, our aim was to test the local and systemic effectiveness of the approach in tree syngeneic mouse tumor models and associate it with tumor immune profiles, characterized by tumor mutational burden, immune infiltration and expression of PD-L1 and MHC-I on tumor cells. While none of the tested characteristic proved predictive for local effectiveness, high tumor mutational burden, immune infiltration and MHC-I expression were associated with higher abscopal effectiveness. Hence, we have confirmed that both the abundance and presentation of tumor antigens as well as the absence of immunosuppressive mechanisms are important for effective in situ vaccination. These findings provide important indications for future development of in situ vaccination based treatments, and for the selection of tumor types that will most likely benefit from it.
Ključne besede: in situ vaccination, gene electrotransfer, interleukin 12, tumor necrosis factor [alfa]
Objavljeno v DiRROS: 19.09.2022; Ogledov: 2643; Prenosov: 751
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10. 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: 2053; Prenosov: 732
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