BACKGROUND: The aim of this study was to evaluate the significance of testing the gain of chromosome 8 and the gain of chromosome 6 as prognostic markers in histopathological samples of enucleated eyes in with uveal melanoma. METHODS: This is a retrospective study of 54 enucleated eyes. The status of chromosomes 3, 8 and 6 was tested by CISH, and FISH was used in a few samples. A follow-up for the detection of metastases was conducted in all patients. The statistical significance of chromosomal abnormalities as a prognostic factor for the development of metastases was determined. RESULTS: The study group consists of 54 patients (average age 63 years), 28 men (51.9%) Monosomy 3 together with gain of chromosome 8 was found in 10 samples (18.5%). Both chromosomal abnormalities were detected in 6 (11%) patients. No chromosomal abnormality in 3 or 8 was detected in 21 (38.9%) patients. Abnormalities of chromosome 6 were present in 6 (11%) patients. Progression free survival after 5 years was 33.3% (95% CI 0.0; 83.3) in these patients. CONCLUSIONS: Our findings indicate a correlation between progression-free survival and the presence of changes in chromosome 3 and e 8 in uveal melanomas. The results underline the necessity of testing for both chromosomal aberrations.
- Klíčová slova
- CISH, FISH, chromosome 6, chromosome 8, progression free survival, uveal melanoma,
- Publikační typ
- časopisecké články MeSH
AIM: The aim of this cytogenetic study is to confirm the significance of chromosome 3 loss (monosomy 3) and of the gain of chromosome 8 as prognostic markers in histopathological samples of enucleated eyes with uveal melanoma in the Czech population. METHODS: This is a retrospective study of 52 enucleated eyes. Chromosome 3 and 8 status were tested by CISH, and in a few samples FISH was used. The correlation between monosomy 3 and gain of chromosome 8 and clinical features (histopathological type, size of the tumour) were evaluated. A follow up for the detection of metastases was conducted in all patients. The statistical significance of chromosomal abnormalities as a prognostic factor for the development of metastases was calculated. RESULTS: There were 52 patients, 27 men (51.9%) and 25 women (48.1%) enrolled in our study group. The mean age was 63 ± 14 years. Loss of the one copy of chromosome 3 (monosomy 3) was detected in 26 (50.0%) patients, monosomy 8 was present in 34.6% of patients with monosomy 3. After 5 years there were no metastases in 82% of patients without monosomy 3 as opposed to 40% of patients with monosomy 3. We confirmed a statistically significant association between progression free survival (PFS) and the presence of monosomy 3 (P=0.017). The association between PFS and gain of chromosome 8 was significant as well (0.010). CONCLUSIONS: Our data showed the association of progression-free survival with the presence of monosomy 3 in uveal melanomas. We provided a good prognostic value of monosomy 3 in uveal melanoma.
- Klíčová slova
- CISH, FISH, chromosome 3, chromosome 8, progression-free survival, uveal melanoma,
- MeSH
- chromozomální aberace * MeSH
- genetická predispozice k nemoci MeSH
- genetické markery * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 3 * MeSH
- lidské chromozomy, pár 8 * MeSH
- melanom genetika MeSH
- monozomie genetika MeSH
- nádory uvey genetika MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- genetické markery * MeSH
Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations of MYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-150, which was uniformly downmodulated in all examined tFLs (∼3.5-fold), and observed that high levels of MYC are responsible for repressing miR-150 in tFL by binding in its upstream region. This MYC-mediated repression of miR-150 in B cells is not dependent on LIN28A/B proteins, which influence the maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also demonstrated that low miR-150 levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-κB signaling in malignant B cells. We revealed that low levels of miR-150 and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that miR-150 could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of the MYC/miR-150/FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.
- MeSH
- aktivace transkripce MeSH
- difúzní velkobuněčný B-lymfom genetika patologie MeSH
- down regulace MeSH
- folikulární lymfom diagnóza genetika patologie MeSH
- forkhead transkripční faktory genetika MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádorová transformace buněk genetika patologie MeSH
- prognóza MeSH
- protoonkogenní proteiny c-myc genetika MeSH
- regulace genové exprese u nádorů * MeSH
- represorové proteiny genetika MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- forkhead transkripční faktory MeSH
- FOXP1 protein, human MeSH Prohlížeč
- mikro RNA MeSH
- MIRN150 microRNA, human MeSH Prohlížeč
- protoonkogenní proteiny c-myc MeSH
- represorové proteiny MeSH
Mutations and deletions of the tumor suppressor TP53 gene are the most frequent genetic alterations detected in human tumors, though they are rather less frequent in lymphomas. However, acquisition of the TP53 mutation was demonstrated to be one of the characteristic markers in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) and prognostic value of the TP53 status has been recognized for these diseases. We present the complex analysis of the TP53 aberrations in 57 cases of MCL and 131 cases of DLBCL. The TP53 status was determined by functional analyses in yeast (FASAY) followed by cDNA and gDNA sequencing. The level of the p53 protein was assessed by immunoblotting and loss of the TP53-specific locus 17p13.3 was detected by FISH. Altogether, we detected 13 TP53 mutations among MCL cases (22.8%) and 29 TP53 mutations in 26 from 131 DLBCL cases (19.8%). The ratio of missense TP53 mutations was 76.9% in MCL and 82.8% in DLBCL. The frequency of TP53 locus deletion was rather low in both diseases, reaching 9.3% in MCL and 15.3% in DLBCL. The presence of TP53 mutation was associated with shorter overall survival (OS) and progression-free survival (PFS) in MCL. Among DLBCL cases, the TP53 mutations shortened both OS and PFS of patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and decreased both OS and PFS of patients with secondary DLBCL disease.
- MeSH
- cyklofosfamid aplikace a dávkování MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie genetika patologie MeSH
- dospělí MeSH
- doxorubicin aplikace a dávkování MeSH
- Kaplanův-Meierův odhad MeSH
- kvasinky genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom z plášťových buněk farmakoterapie genetika patologie MeSH
- mutace MeSH
- nádorový supresorový protein p53 genetika MeSH
- prednison aplikace a dávkování MeSH
- přežití bez známek nemoci MeSH
- prognóza * MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- rituximab aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vinkristin aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklofosfamid MeSH
- doxorubicin MeSH
- nádorový supresorový protein p53 MeSH
- prednison MeSH
- rituximab MeSH
- TP53 protein, human MeSH Prohlížeč
- vinkristin MeSH
D-type cyclins are involved in cell cycle regulation and play an important role in the pathogenesis of lymphomas. Aberrant expression of cyclin D1 is associated with mantle cell lymphoma (MCL) and serves as a diagnostic marker of MCL. Analysis of cyclin D expression in tumor tissues of patients with diffuse large B-cell lymphoma (DLBCL) which comprises a heterogeneous group of tumors may contribute to their stratification. We analyzed expression of cyclin D1, D2, and D3 mRNAs in 30 MCL and 104 DLBCL patients using qRT-PCR and addressed their significance for disease outcome. We confirmed a high level of cyclin D1 mRNA in 29 MCL cases (97%). One case (3%) was identified as positive for cyclin D2. Expression of cyclin D1 was limited to MCL and did not occur in DLBCL. Overexpression of cyclin D2, which is rare in MCL, occurred more frequently in DLBCL (11 cases, 10.6%). We showed that high expression of cyclin D2 in DLBCL cases de novo decreased the overall survival rate (P=0.016) and progression-free survival (P=0.009). The expression pattern of cyclin D3 was similar in both types of studied lymphomas and it did not affect the disease outcome.
- MeSH
- cyklin D genetika metabolismus MeSH
- difúzní velkobuněčný B-lymfom metabolismus mortalita MeSH
- exprese genu MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom z plášťových buněk metabolismus mortalita MeSH
- nádorové biomarkery genetika metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cyklin D MeSH
- nádorové biomarkery MeSH
Lung cancer is the leading cause of cancer-related deaths worldwide. The p53 tumor suppressor is a transcription factor controlling expression of its target genes in response to various stress stimuli. Mutations of the TP53 gene occur very frequently in lung carcinomas and they play an important role in both oncogenic transformation of lung epithelial cells and lung carcinoma progression. We determined the TP53 status in 42 samples of squamous cell lung carcinoma (SQCC) and 56 samples of lung adenocarcinoma (AC) by the functional analysis FASAY and its variant called split assay. Altogether, we detected 64 TP53 mutations in 63 patients and analyzed them by cDNA and gDNA sequencing. The TP53 mutations were found in 76.2% (32/42) of SQCC cases, and 55.4% (31/56) of ACs. Immunoblotting revealed the p53 protein accumulation in 18 samples (42.9%) among SQCC cases and 19 samples (33.9%) among AC cases. Using fluorescence in situ hybridization we detected loss of the TP53-specific 17p13.3 locus in 23 from 41 analyzed SQCC samples (56.1%) and in 20 from 54 analyzed AC samples (37.0%). We did not find any statistically significant differences in overall and disease-free survival in relation to TP53 status.
- MeSH
- adenokarcinom plic MeSH
- adenokarcinom genetika patologie MeSH
- dospělí MeSH
- hybridizace in situ fluorescenční MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádorová transformace buněk genetika MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory plic genetika patologie MeSH
- nemalobuněčný karcinom plic genetika patologie MeSH
- přežití bez známek nemoci MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- spinocelulární karcinom genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorový supresorový protein p53 MeSH
