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Povzetek: Background. Clonality determination in patients with lymphoproliferative disorders can improve the final diagnosis.The aim of our study was to evaluate the applicative value of standardized BIOMED-2 gene clonality assay protocolsfor the analysis of clonality of lymphocytes in a group of different lymphoid proliferations.Materials and methods. With this purpose, 121 specimens from 91 patients with suspected lymphoproliferationssubmitted for routine diagnostics from January to December 2011 were retrospectively analyzed. According to thefinal diagnosis, our series comprised 32 cases of B-cell lymphomas, 38 cases of non-Hodgkins T-cell lymphomas and51 cases of reactive lymphoid proliferations. Clonality testing was performed using the BIOMED-2 clonality assays.Results. The determined sensitivity of the TCR assay was 91.9%, while the sensitivity of the IGH assay was 74.2%. Thedetermined specificity of the IGH assay was 73.3% in the group of lymphomas and 87.2% in the group of reactivelesions. The determined specificity of the TCR assay was 62.5% in the group of lymphomas and 54.3% in the group ofreactive lesions.Conclusions. In the present study, we confirmed the utility of standardized BIOMED-2 clonality assays for the detectionof clonality in a routine diagnostical setting of non-Hodgkins lymphomas. Reactions for the detection of thecomplete IGH rearrangements and reactions for the detection of the TCR rearrangements are a good choice forclonality testing of a wide range of lymphoid proliferations and specimen types while the reactions for the detectionof incomplete IGH rearrangements have not shown any additional diagnostic value.
Ključne besede: Biomed-2, clonality analysis, lymphomas, IGH rearrangement, TCR rearrangement
Objavljeno v DiRROS: 11.04.2024; Ogledov: 55; Prenosov: 17
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Povzetek: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
Ključne besede: early breast cancer, polygenic risk score, risk prediction
Objavljeno v DiRROS: 21.03.2024; Ogledov: 73; Prenosov: 26
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Ključne besede: genetsko testiranje
Objavljeno v DiRROS: 29.09.2022; Ogledov: 600; Prenosov: 140
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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: 465; Prenosov: 238
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Povzetek: Mutacija V600E predstavlja več kot 90 % vseh opisanih mutacij v genu BRAF pri različnih vrstah tumorjev. Protein, ki nastane kot produkt onkogena BRAF z mutacijo V600E (BrafV600E), sproža nenehno signaliziranje prek signalne poti RAS-RAF-MAPK, kar povzroči številnejše delitve celice in njeno maligno transformacijo. Zato ima onkogen BrafV600E pomembno vlogo pri indukciji in napredovanju tumorja ter verjetno predstavlja zgodnji dogodek v procesu maligne transformacije. Po podatkih iz literature je čezmerno izražen v različnih vrstah solidnih tumorjev, kot so melanom, metastatski rak debelega črevesa in danke, papilarni rak ščitnice, rak ledvic (RCC), hepatocelularni karcinom (HCC), velikocelični rak pljuč (NSCLC) in serozni rak jajčnikov. Na Oddelku za molekularno diagnostiko smo uvedli metodo za določanje mutacije V600E v genu BRAF. Metoda temelji na PCR-pomnoževanju in uporabi specifičnih sond. Izkazala se je kot primerna za rutinsko diagnostiko. V primerjavi z neposrednim sekveniranjem, ki velja za zlati standard, sta bili njeni občutljivost in specifičnost 100-odstotni. Zaradi velike specifičnosti je zanesljiva za ločevanje med normalnim in mutiranim genotipom BRAF in je primerna za hitro rutinsko diagnostiko.
Objavljeno v DiRROS: 31.08.2018; Ogledov: 2960; Prenosov: 658
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