BACKGROUND: The TMPRSS2-ERG gene fusion is one of the most widely spread chromosomal rearrangements in carcinomas. Since its discovery, a number of studies have examined its diagnostic, prognostic and therapeutic implications for prostate cancer where suitable biomarkers are still lacking. The publication data are inconsistent. The aim of this review was to critically evaluate the current clinical impact of this gene fusion. METHODS: The PubMed online database was used to search relevant reviews and original articles. RESULTS: Although the TMPRSS2-ERG gene fusion appears to be a suitable diagnostic biomarker, the prognostic implications of this gene fusion are still unclear. Several new strategies for therapeutically targeting ETS fusions and their modulators have been identified and are currently being investigated. CONCLUSION: Due to the heterogeneity of prostate cancer, the combination of several biomarkers is necessary to accurately assess the presence of prostate cancer, predict its potential clinical outcome and decide on appropriate therapy (e.g. PARP inhibitors).

• MeSH
• fúze genů genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory prostaty diagnóza   genetika   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery MeSH
• TMPRSS2-ERG fusion protein, human MeSH Prohlížeč

BACKGROUND: The aim of the study was to detect CD204 + and CD3 + cells in the infiltrate of benign prostatic hyperplasia, prostatic intraepithelial neoplasia and prostatic cancer in prostate specimens after radical prostatectomy. Another goal was to determine correlation of the intensity of the infiltration with ERG oncoprotein expression as well as with the presence of activat-ing translocation TMPRSS2-ERG. MATERIALS AND METHODS: To confirm the translocation, we used fluorescence in situ hybridization. Imunohistochemistry was used to detect the presence of ERG oncoprotein and for assesment of the number of CD204+ and CD3+ infiltrat-ing cells. We determined the capability to infiltrate malignant structures accord-ing to differences in infiltration of benign and malignant prostate structures. RESULTS: Biometric analysis confirmed that the number of CD204+ macrophages in the malignant structure was significantly higher than in the benign prostatic hyperplasia regardless of the fusion pattern. Increased infiltration by CD3+ cells was only detected in malignant structures of the prostate in a group with normal signal pattern and in a group with TMPRSS2-ERG fusion. Expression of ERG positively correlated with CD204+ and CD3+ cells infiltration of malignant structures only in cases where the TMPRSS2-ERG fusion was found. In the group with a break in the TMPRSS2 gene, a positive correlation was only found between ERG expression and CD204+ macrophages infiltration. In cases with a normal signal pattern, no correlation was found. In the group with TMPRSS2-ERG fusion we observed significantly more cases with a good capability of CD204+ cells to infiltrate malignant structures, unlike the group with a normal signal pattern, where there were more cases with the weak reactivity of CD204 + cells to infiltrate the malignant structures. The same was observed for CD3+ cells. CD204+ macrophages and CD3+ T-lymphocytes in the group with TMPRSS2-ERG gene fusion, infiltrated the malignant prostate structures more intensely, but their effect on malignant transformation may be different. CONCLUSIONS: The association between the presence of the TMPRSS2-ERG fusion and the different capability of inflammatory cells to infiltrate malignant structures has not been reported so far. The results confirm the important role of the activated ERG gene, due to TMPRSS2-ERG fusion, in the development of inflammation of the prostate as well as the effect of inflammatory cells on the course of neoplastic process. This leads to considerations about introduc-ing immunomodulatory modalities into prostate cancer therapeutic protocols. Key words: prostate cancer - TMPRSS2-ERG gene fusion - ERG - immune response - CD204+ macrophages - CD3+ T-lymphocytes.

• Klíčová slova
• prostate cancer -  TMPRSS2-ERG gene fusion -  ERG -  immune response -  CD204+ macrophages -  CD3+ T-lymphocytes,
• MeSH
• antigeny CD3 MeSH
• fúze genů MeSH
• fúzní onkogenní proteiny metabolismus   MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• nádory prostaty farmakoterapie   imunologie   metabolismus   chirurgie   MeSH
• scavengerové receptory - třída A MeSH
• T-lymfocyty imunologie   MeSH
• transkripční regulátor ERG metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD3 MeSH
• ERG protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• MSR1 protein, human MeSH Prohlížeč
• scavengerové receptory - třída A MeSH
• TMPRSS2-ERG fusion protein, human MeSH Prohlížeč
• transkripční regulátor ERG MeSH

Congenital mesoblastic nephroma (CMN), the most common renal tumor of infancy, is a mesenchymal neoplasm histologically classified into classic, cellular, or mixed types. Most cellular CMNs harbor a characteristic ETV6-NTRK3 fusion. Here, we report an unusual congenital mesoblastic nephroma presenting in a newborn boy with a novel EML4-ALK gene fusion revealed by Anchored Multiplex RNA Sequencing Assay. The EML4-ALK gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital mesoblastic nephroma, with yet another example of kinase oncogenic activation through chromosomal rearrangement. The methylation profile of the tumor corresponds with infantile fibrosarcoma showing the biological similarity of these two entities.

• Klíčová slova
• ALK fusion, RNAseq, congenital mesoblastic nephroma, infantile fibrosarcoma, methylation profiling,
• MeSH
• fibrosarkom diagnóza   genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• mezoblastický nefrom diagnóza   genetika   patologie   MeSH
• novorozenec MeSH
• protein ETS, translokační varianta 6 MeSH
• protoonkogenní proteiny c-ets genetika   MeSH
• receptor trkC genetika   MeSH
• represorové proteiny genetika   MeSH
• sekvenování transkriptomu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• EML4-ALK fusion protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• NTRK3 protein, human MeSH Prohlížeč
• protoonkogenní proteiny c-ets MeSH
• receptor trkC MeSH
• represorové proteiny MeSH

BACKGROUND/AIM: Current research of prostate cancer (PCa) offers a promising way of identifying patients with adverse prognosis who do benefit from radical treatment that can affect quality of life as resections are associated with numerous side-effects. The aim of our study was to evaluate the relationship of TMPRSS2-ERG fusion gene status, tumor tissue prostate-specific antigen (PSA), prostate cancer antigen 3 (PCA3), miR-23b, miR-26a and miR-221 expression levels in combination with preoperative serum PSA level to the risk of PCa recurrence after radical prostatectomy. PATIENTS AND METHODS: The study group consisted of 108 patients who underwent radical prostatectomy. PSA was measured in peripheral blood collected preoperativelly. The expression of TMPRSS2-ERG transcript and the expression of miR-23b, miR-26a and miR-221 in formalin-fixed, paraffin-embedded (FFPE) tumor tissues was analyzed by reverse transcription (RT) real-time polymerase chain reaction (PCR). RESULTS: Significantly shorter time to recurrence was observed in patients with high expression of TMPRSS2-ERG (p=0.0020). High levels of preoperative PSA (>10.0 ng/ml) proved to be marker of shorter time to recurrence (p=0.0153). The most promising marker of the risk of recurrence after radical prostatectomy was a combination of high level of preoperative serum PSA and high expression of TMPRSS2-ERG fusion transcript in tumor tissue (p=0.0001). CONCLUSION: A combination of high preoperative serum PSA and high expression of TMPRSS2-ERG could be promising in distinguishing those tumors that are aggressive and life-threatening.

• Klíčová slova
• PCA3, PSA, Prostate cancer, TMPRSS2-ERG, microRNA, prognosis,
• MeSH
• antigeny nádorové biosyntéza   genetika   MeSH
• dospělí MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru krev   genetika   patologie   MeSH
• mikro RNA biosyntéza   genetika   MeSH
• nádorové biomarkery biosyntéza   krev   genetika   MeSH
• nádory prostaty krev   genetika   patologie   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• prostata patologie   MeSH
• prostatektomie MeSH
• prostatický specifický antigen krev   MeSH
• regulace genové exprese u nádorů MeSH
• rizikové faktory MeSH
• senioři MeSH
• zalévání tkání do parafínu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• fúzní onkogenní proteiny MeSH
• mikro RNA MeSH
• MIRN221 microRNA, human MeSH Prohlížeč
• MIRN23a microRNA, human MeSH Prohlížeč
• MIRN26A microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• prostate cancer antigen 3, human MeSH Prohlížeč
• prostatický specifický antigen MeSH
• TMPRSS2-ERG fusion protein, human MeSH Prohlížeč

We report a unique case of aleukemic granulocytic sarcoma of the neck, originally misdiagnosed as non-Hodgkin's lymphoma (NHL), though chloroma was also suspected due to a greenish macroscopic appearance and the presence of myeloid chloroacetate esterase (CAE)+ cells. The proof of clonal T cell receptor gamma chain (TcRgamma) gene rearrangements in the recurring tumor was deemed to confirm the initial diagnosis of T cell NHL. Altogether five distinct types of clonal TcRgamma gene rearrangements were found in the tumor, bone marrow and peripheral blood. Only retrospectively, using RT-PCR, did we detect the acute myeloid leukemia subset-specific fusion gene AML1/ETO in the frozen samples of the relapsed tumor, as well as in the otherwise unaffected bone marrow and peripheral blood (representing 'minimal initial disease' in the latter two samples). Simultaneous staining verified that the neoplastic CAE+ cells and CD45RO+ T cells were different populations.

• MeSH
• dospělí MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba - gama řetězec receptoru antigenů T-buněk * MeSH
• lidé MeSH
• myeloidní sarkom genetika   imunologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protein PEBP2A2 MeSH
• protein RUNX1T1 MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AML1-ETO fusion protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• protein PEBP2A2 MeSH
• protein RUNX1T1 MeSH
• transkripční faktory MeSH

Acute leukemia is considered to be a two- or multiple-step process. Although there is a considerable knowledge regarding the character of the "first hit," the nature of the "second hit" remains unanswered in most of the cases including leukemias with MLL gene rearrangement. We demonstrate here a striking sequence of events, which include a covert, protracted preleukemic phase characterized by a dominant MLL/FOXO3A clone with intact myeloid differentiation and the subsequent acquisition of a secondary genetic abnormality, leading to overt lymphoblastic leukemia. Backtracking of the secondary acute lymphoblastic leukemia (sALL) with the MLL rearrangement showed no blasts in the bone marrow (BM) during the protracted preleukemic phase. However, at the same time (more than 1 year before the sALL diagnosis) the MLL/FOXO3A was present in up to 90% of BM cells including myeloid lineage, suggesting that the fusion arose in a multipotent progenitor. To identify potential "second hit" precipitating sALL we compared DNA in preleukemic versus fully leukemic samples. The analysis revealed a 10 Mb gain on 19q13.32 in the sALL, absent in the preleukemic specimen. These data provide insight into the dynamics of leukemogenesis in secondary leukemia with MLL rearrangement.

• MeSH
• akutní promyelocytární leukemie genetika   metabolismus   patologie   terapie   MeSH
• cytogenetické vyšetření MeSH
• forkhead transkripční faktory genetika   metabolismus   MeSH
• fúze genů * MeSH
• genová přestavba MeSH
• histonlysin-N-methyltransferasa MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• lidské chromozomy, pár 19 genetika   MeSH
• mladiství MeSH
• myeloidní buňky metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové kmenové buňky metabolismus   patologie   MeSH
• pre-B-buněčná leukemie genetika   metabolismus   patologie   terapie   MeSH
• preleukemie genetika   MeSH
• protein FOXO3 MeSH
• protoonkogenní protein MLL genetika   metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXO3 protein, human MeSH Prohlížeč
• histonlysin-N-methyltransferasa MeSH
• KMT2A protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein FOXO3 MeSH
• protoonkogenní protein MLL MeSH

We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a positive result and, therefore, the patient was treated with crizotinib with a good therapeutic response. However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.

• Klíčová slova
• ATRNL1, Crizotinib, EML4-ALK, Lung cancer, NSCLC, Targeted therapy,
• MeSH
• fúzní onkogenní proteiny chemie   genetika   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• inzerční mutageneze * MeSH
• krizotinib MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• nádory plic diagnóza   farmakoterapie   genetika   MeSH
• nemalobuněčný karcinom plic diagnóza   farmakoterapie   genetika   MeSH
• pyrazoly terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• rentgendiagnostika hrudníku MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• EML4-ALK fusion protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• inhibitory proteinkinas MeSH
• krizotinib MeSH
• pyrazoly MeSH
• pyridiny MeSH

ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. Although numbers were small, correlating the clinico-pathologic features of the 4 ETV6-X fusion tumors and 5 MASC cases with atypical fusion transcripts raises the possibility of that they may behave more aggressively.

• MeSH
• diagnostické techniky molekulární * MeSH
• dospělí MeSH
• fúze genů * MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genetická predispozice k nemoci MeSH
• genová přestavba * MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz chemie   genetika   patologie   terapie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• protein ETS, translokační varianta 6 MeSH
• protoonkogenní proteiny c-ets genetika   MeSH
• registrace MeSH
• represorové proteiny genetika   MeSH
• sekreční karcinom mamárního typu chemie   genetika   patologie   terapie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ETV6-NTRK3 fusion protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-ets MeSH
• represorové proteiny MeSH

INTRODUCTION: This study presents a novel molecular parameter potentially co-defining tumor biology-the total tumor suppressor gene (TSG) count at chromosomal loci harboring genes rearranged in fusion-defined tumors. It belongs to the family of molecular parameters created using a black-box approach. METHOD: It is based on a public curated Texas TSG database. Its data are regrouped based on individual genes loci using another public database (Genecards). The total TSG count for NTRK (NTRK1; OMIM: 191315; NTRK2; OMIM: 600456; NTRK3; OMIM: 191316), NRG1 (OMIM: 142445), and RET (OMIM: 164761) rearranged tumors in patients treated with a theranostic approach is calculated using the results of recently published studies. RESULTS: Altogether 138 loci containing at least three TSGs are identified. These include 21 "extremely hot" spots, with 10 to 28 TSGs mapping to a given locus. However, the study falls short of finding a correlation between tumor regression or patient survival and the TSG count owing to a low number of cases meeting the study criteria. CONCLUSION: The total TSG count alone cannot predict the biology of translocation-defined tumors. The addition of other parameters, including microsatellite instability (MSI), tumor mutation burden (TMB), homologous recombination repair deficiency (HRD), and copy number heterogeneity (CNH), might be helpful. Thus a multi-modal data integration is advocated. We believe that large scale studies should evaluate the significance and value of the total TSG count.

• Klíčová slova
• artificial intelligence, cancer, chromosomal instability, chromothripsis, copy number heterogeneity, gene, gene rearrangement, homologous recombination repair, microsatellite instability, translocation, tumor mutation burden, tumor suppressor gene,
• MeSH
• fúze genů MeSH
• genomika MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• nádory * genetika   patologie   MeSH
• translokace genetická MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH

AIMS: This retrospective non-randomised study aims to identify new and rare fusion partners with USP6 in the setting of nodular fasciitis. It has been proven, that nodular fasciitis can harbour different variants of USP6 fusions, which can be used in routine diagnostics and even determine the biological behaviour of the process. METHODS: A total of 19 cases of nodular fasciitis examined between 2011 and 2022 at Motol University Hospital in Prague were included into this study. Next to the histopathological evaluation, all cases were assessed using immunohistochemistry, RT-PCR and Anchored multiplex RNA methods. Patient's main demographic characteristics and corresponding clinical data were also analysed. RESULTS: This study presents one novel (KIF1A) and five rare examples (TMP4, SPARC, EIF5A, MIR22HG, COL1A2) of fusion partners with USP6 among 19 cases of nodular fasciitis. CONCLUSION: Identification of USP6 fusion partners in nodular fasciitis helps to understand the biology of such lesions. Moreover, it can be useful in routine histopathological practice of soft-tissues diagnostics, especially in preventing possible misdiagnosis of malignancy.

• Klíčová slova
• Pathology Department, Hospital, Pathology, Molecular, Soft Tissue Neoplasms,
• MeSH
• dospělí MeSH
• fasciitida * genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba * MeSH
• imunohistochemie MeSH
• kineziny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• senioři MeSH
• thiolesterasa ubikvitinu * genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• USP6 protein, human MeSH Prohlížeč