1. Imunski fenotipi v mikrookolju primarnega tumorja in jetrnih zasevkov pri bolnici s silovitim razsojem vnetnega, trojno negativnega raka dojke v jetra med neoadjuvantnim zdravljenjem s citostatiki in zaviralcem imunskih kontrolnih točkMarina Mencinger, Snežana Pavlović Djokić, Vida Stegel, Srdjan Novaković, Juan Antonio Contreras, Andreja Klevišar Ivančič, 2022, objavljeni povzetek strokovnega prispevka na konferenci Ključne besede: onkologija, rak dojke, kemoterapija
Objavljeno v DiRROS: 03.02.2023; Ogledov: 71; Prenosov: 24
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2. Genetsko testiranje pri raku prostateVida Stegel, Srdjan Novaković, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Rak prostate je v svetovnem merilu drugi najpogostejši rak pri moških. Genetski dejavniki lahko pomembno zvišajo tveganje za rak prostate. Genetsko testiranje na zarodne patogene različice v genih BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6 in PMS2 se izvaja za ocenjevanje ogroženosti bolnika, da zboli za drugimi raki, in za oceno ogroženosti njegovih družinskih članov. Pri metastatskem raku prostate se za zdravljenje uporabljajo tarčna zdravila, kot so zaviralci poli-ADP-riboza polimeraze (PARP) in imunoterapija. Obe vrsti zdravil sta dokazano bolj učinkoviti pri delovanju na tumorje s specifičnimi okvarami v genih, ki so soudeleženi v mehanizmih za popravljanje napak na DNA, t. j. homologne rekombinacije (HR) ali popravljanje neujemanj baz (MMR). Zato molekularnogenetsko testiranje tumorjev bolnikov z rakom prostate uporabljamo za določanje okvar HR in okvar v genih MMR. Kot pomoč pri natančnejši opredelitvi lokaliziranega raka prostate in sub-klasifikaciji glede na verjetnost napredovanja bolezni se v zadnjem času preizkušajo tudi molekularnogenetske preiskave, ki temeljijo na merjenju ekspresije različnih genov v kombinaciji z drugimi kliničnimi in histopatološkimi dejavniki.
Ključne besede: rak prostate, genetsko testiranje, diagnostika
Objavljeno v DiRROS: 02.02.2023; Ogledov: 62; Prenosov: 25
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3. Pomen PIK3CA aktivirajočih mutacij za izid bolezni pri bolnicah z invazivnim lobularnim karcinomom dojke, zdravljenih z dopolnilno endokrino terapijoDomen Ribnikar, Valentina Jerič Horvat, Ivica Ratoša, Zachary Veitch, Biljana Grčar-Kuzmanov, Srdjan Novaković, Erik Langerholc, Maja Pohar Perme, Eitan Amir, Boštjan Šeruga, 2022, objavljeni povzetek strokovnega prispevka na konferenci Ključne besede: onkologija, rak dojke, kemoterapija
Objavljeno v DiRROS: 27.01.2023; Ogledov: 61; Prenosov: 30
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4. Molekularna diagnostika raka dojkSrdjan Novaković, 2022, objavljeni strokovni prispevek na konferenci Povzetek: Rak je bolezen, ki nastane kot posledica delovanja številnih dejavnikov (genetskih, okoljskih, življenjskega sloga), ki povzročijo maligno spremembo celice. S stališča molekularne biologije in genetike razlikujemo dedne in sporadične oblike raka. Genetske spremembe, ki jih opredeljujemo z metodami molekularne diagnostike, nam lahko služijo za različne namene: 1. oceno tveganja, da oseba zboli za rakom, 2. natančnejšo opredelitev tumorjev, 3. oceno prognoze bolezni, 4. napoved odgovora na zdravljenje, 5. napoved presnavljanja zdravil, 6. spremljanje odgovora na zdravljenje, 7. godnje odkrivanje ponovitve bolezni. V tem prispevku podajam osnovni pregled uporabe molekularne diagnostike pri raku dojk. Prispevek vključuje molekularno diagnostiko dednih oblik raka in molekularno diagnostiko sporadičnih oblik raka glede na trenutno veljavne mednarodne smernice.
Ključne besede: rak dojk, diagnostika, onkologija
Objavljeno v DiRROS: 22.12.2022; Ogledov: 80; Prenosov: 29
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7. Treatment outcomes and relative dose intensity of chemotherapy in patients with advanced Hodgkin lymphomaSamo Rožman, Barbara Jezeršek Novaković, Nina Ružić Gorenjec, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: The present retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of patients with advanced stage Hodgkin lymphoma (HL) receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimens (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 patients with HL treated between 2004 and 2013 were enrolled for evaluation. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, and the majority were male and had stage IV disease. A total of 54 patients received ABVD and 60 received BEACOPP chemotherapy with 24 and four deaths, respectively. Patients in the BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) and better performance status in comparison with the ABVD group, making the comparison of groups not possible. In the ABVD group, RDI was not significantly associated with OS (P=0.590) or PFS (P=0.354) in a multivariate model where age was controlled. The low number of events prevented this analysis in the BEACOPP group. The age of patients was strongly associated with both OS and PFS; all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI, performance status) lost their effect in multivariate analyses where age was controlled. Based on these observations, it was concluded that RDI was not associated with OS or PFS after age is controlled, neither in all patients combined nor in the ABVD group.
Ključne besede: Hodgkin lymphoma, chemotherapy, outcome, primary treatment
Objavljeno v DiRROS: 23.09.2022; Ogledov: 221; Prenosov: 75
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8. Trends and timing of risk-reducing mastectomy uptake in unaffected BRCA1 and BRCA2 carriers in SloveniaTaja Ložar, Janez Žgajnar, Andraž Perhavec, Ana Blatnik, Srdjan Novaković, Mateja Krajc, 2021, izvirni znanstveni članek Povzetek: Objectives. Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia. Materials and Methods. Female BRCA carriers without personal history of cancer were included in the study. Clinical data on PV/LPV type, date of RRM, type of reconstructive procedure, occult carcinoma and histopathology results was collected and analyzed. Results. Of the 346 unaffected BRCA carriers (median age 43 years, 70% BRCA1, 30% BRCA2, median follow-up 46 months) who underwent genetic testing between October 1999 and December 2019, 25.1% had a RRM (range 35-50 years, median age at surgery 38 years). A significant difference in time to prophylactic surgery between women undergoing RRM only vs. women undergoing RRM combined with risk-reducing salpingo-oophorectomy was observed (22.6 vs 8.7 months, p=0.0009). We observed an upward trend in the annual uptake in line with the previously observed Angelina Jolie effect. In 5.7% of cases, occult breast cancer was detected. No women developed breast cancer after RRM. Women who did not opt for surgical prevention developed BRCA1/2-related cancers (9.3%). Conclusion. The uptake of RRM among unaffected BRCA carriers is 25.1% and is similar to our neighboring countries. No women developed breast cancer after RRM while women who did not opt for surgical prevention developed BRCA1/2 related cancers in 9.3% of cases. The reported data may provide meaningful aid for carriers when deciding on an optimal prevention strategy.
Ključne besede: risk-reducing mastectomy, breast cancer, BRCA
Objavljeno v DiRROS: 21.09.2022; Ogledov: 157; Prenosov: 61
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9. 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: 149; Prenosov: 97
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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: 161; Prenosov: 78
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