Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.

• MeSH
• autologní transplantace MeSH
• dospělí MeSH
• lenalidomid aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   mortalita   terapie   patologie   MeSH
• prognóza MeSH
• průtoková cytometrie * metody   MeSH
• retrospektivní studie MeSH
• reziduální nádor * diagnóza   MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Mezoblastický nefrom je nejčastější tumor ledvin u novorozenců a kojenců do 3 měsíců věku. Existují tři subtypy mezoblastického nefromu: klasický, celulární a smíšený. Jedná se o většinou benigní tumor, avšak celulární subtyp může vykazovat známky agresivního chování. Tato kazuistika popisuje případ pacienta s celulárním subtypem tumoru s patrnou heterogenní strukturou, cystickými okrsky a podle histologie s infiltrací okolní tukové tkáně a perineurální propagací. U pacienta byla při cytogenetickém vyšetření také prokázána fúze genů ETV6-NTRK3, která je typická pro celulární variantu a umožňuje její odlišení od varianty klasické. Léčba je chirurgická, volí se radikální nefrektomie, u vyšších stadií celulární varianty je doporučena také adjuvantní chemoterapie. Diferenciálně diagnosticky je problematické odlišení od maligního Wilmsova tumoru, existují charakteristiky spíše typické pro jednotlivé tumory, avšak spolehlivé odlišení bohužel není pomocí zobrazovacích metod vždy možné a diagnózu lze stanovit až pomocí histologického vyšetření.

Mesoblastic nephroma is the most common renal tumor in the neonatal period and infants less than three months old. There are three subtypes of mesoblastic nephroma: classic, cellular and mixed. It is mostly a benign tumor, although the cellular subtype may show signs of aggressive behavior. This case report describes a patient with a cellular subtype with heterogeneous structure, cystic degeneration and, according to histology, infiltration of the surrounding adipose tissue and perineural propagation. Cytogenetics also revealed the ETV6-NTRK3 gene fusion, which is typical for the cellular variant and allows its differentia- tion from the classic variant. The treatment of choice is surgical resection, adjuvant chemotherapy is advised for higher stages of cellular variant. Differential diagnosis from Wilms tumor is problematic, there are characteristics relatively typical for individual tumors, but absolute distinction is unfortunately not always possible by diagnostic imaging and the diagnosis can only be established by histological examination.

The purpose of this study is to elucidate the genetic causes and phenotypic presentation of nonfamilial tall stature (nFTS) and to compare these findings with those of familial tall stature (FTS) from the same population that was previously studied. Children with nFTS (defined as a height > + 2 SDs with both parents' heights < + 2 SDs) underwent endocrine and anthropometric examinations and genetic testing (karyotyping, SHOX gene dosage analysis and next-generation sequencing of 786 growth-associated genes). Exome sequencing was performed in patients with negative genetic results and a height > + 3 SDs. A total of 55 children with nFTS were enrolled. The median height was + 2.8 SD (2.4-3.2 SD), and the median midparental height was + 0.7 SD (0.4-0.9 SD). Genetic causes of tall stature were identified in 6/55 (11%) children. Specifically, four children had gonosomal aneuploidy (47,XXY [2x], 47,XXX, 48,XXXX), one had a heterozygous complex rearrangement including SHOX gene duplication, and one carried a pathogenic variant in the TGFBR2 gene leading to Loeys-Dietz syndrome. A genetic cause of tall stature was significantly less common in nFTS (11%) than in our previously published cohort with FTS (32%). Conclusion: Cytogenetic abnormalities were the predominant genetic alteration identified in children with nFTS, confirming the justification of karyotype analysis in this cohort. The probability of genetic alterations was greater in children with FTS than in those with nFTS. Our findings suggest that the current guidelines for complex investigation are efficient for children with nFTS but need revision in children with FTS. What is known - what is new • Although tall stature is generally considered beneficial, it can be associated with health risks which need to be recognized in time. Tall stature without intellectual impairment is usually considered to be polygenic. • However, the cause of familial tall stature was monogenic more often than it was thought previously. • Children with non-familial and apparently non-syndromic tall stature have never been systematically investigated. • Monogenic causes of non-familial tall stature were observed in 11% of patients, including a participant with Loeys-Dietz syndrome.

• MeSH
• chromozomální aberace * MeSH
• dítě MeSH
• fenotyp MeSH
• genetické testování MeSH
• karyotypizace MeSH
• lidé MeSH
• mladiství MeSH
• poruchy růstu * genetika   MeSH
• předškolní dítě MeSH
• protein SHOX MeSH
• sekvenování exomu MeSH
• tělesná výška * genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus.

• MeSH
• delece genu * MeSH
• homeodoménové proteiny * genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty * genetika   patologie   metabolismus   MeSH
• progrese nemoci MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• transkripční faktory * genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Gemtuzumab ozogamicin je zažitou součástí moderní terapie akutní myeloidní leukemie zásadně zlepšující léčebné výsledky. Jeho využití je nicméně omezeno na pacienty v nízkém a středním cytogenetickém riziku. Další omezení pak přichází s možnou toxicitou tohoto léčivého přípravku, zejména s rizikem rozvoje sinusoidálního obstrukčního syndromu a závažných krvácení. Při jeho používání je třeba pečlivě zvážit poměr risk/benefit.

Gemtuzumab ozogamicin is a standard part of acute myeloid leukemia therapy bringing significant improvement of treatment outcome. However, its use is limited to patients in favorable and intermediate cytogenetic risk groups. Another limitation is brought by possible toxicity especially the risk of sinusoidal obstruction syndrome development or severe bleeding complications. It should only be used after a careful assessment of risk/benefit ratio.

• MeSH
• akutní monocytární leukemie farmakoterapie   MeSH
• gemtuzumab * škodlivé účinky   toxicita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation is believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study in healthy individuals in relation to occupational and smoking-related exposure compared to nonexposed referents. The associations (at P < 10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS, and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis, and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, the expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

• MeSH
• celogenomová asociační studie * MeSH
• chromozomální aberace * MeSH
• interakce genů a prostředí MeSH
• lidé MeSH
• lymfocyty metabolismus   MeSH
• nádory genetika   MeSH
• oprava DNA genetika   MeSH
• poškození DNA MeSH
• pracovní expozice škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cancer cells display complex genomic aberrations that include large-scale genetic rearrangements and epigenetic modulation that are not easily captured by short-read sequencing. This study presents a novel approach for simultaneous profiling of long-range genetic and epigenetic changes in matched cancer samples, focusing on clear cell renal cell carcinoma (ccRCC). ccRCC is a common kidney cancer subtype frequently characterized by a 3p deletion and the inactivation of the von Hippel-Lindau (VHL) gene. We performed integrated genetic, cytogenetic, and epigenetic analyses on paired tumor and adjacent nontumorous tissue samples. Optical genome mapping identified genomic aberrations as structural and copy number variations, complementing exome-sequencing findings. Single-molecule methylome and hydroxymethylome mapping revealed a significant global reduction in 5hmC level in both sample pairs, and a correlation between both epigenetic signals and gene expression was observed. The single-molecule epigenetic analysis identified numerous differentially modified regions, some implicated in ccRCC pathogenesis, including the genes VHL, PRCC, and PBRM1. Notably, pathways related to metabolism and cancer development were significantly enriched among these differential regions. This study demonstrates the feasibility of integrating optical genome and epigenome mapping for comprehensive characterization of matched tumor and adjacent tissue, uncovering both established and novel somatic aberrations.

• MeSH
• DNA vazebné proteiny MeSH
• epigeneze genetická * genetika   MeSH
• epigenom * genetika   MeSH
• karcinom z renálních buněk * genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mapování chromozomů metody   MeSH
• metylace DNA * genetika   MeSH
• nádorový supresorový protein VHL genetika   MeSH
• nádory ledvin * genetika   patologie   MeSH
• regulace genové exprese u nádorů MeSH
• transkripční faktory MeSH
• variabilita počtu kopií segmentů DNA * genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

In previous RENEB interlaboratory comparisons based on the manual scoring of dicentric chromosomes, a tendency for systematic overestimation for doses > 2.5 Gy was found. However, these exercises included only very few doses in the high dose range, and they were heterogeneous in terms of radiation quality and evaluation mode, and comparable only to a limited extent. Here, this presumed deviation was explored by investigating three doses > 2.5 Gy. Blood samples were irradiated (2.56, 3.41 and 4.54 Gy) using a 60Co source and sent to 14 member laboratories of the RENEB network, which performed the dicentric chromosome assay (manual and/or semi-automatic scoring) and reported dose estimates. Most participants provided estimates that agreed very well with the physical reference doses and all provided dose estimates were in the correct clinical category (> 2 Gy). The previously observed tendency for a systematic bias across all laboratories was not confirmed. However, tendencies for systematic underestimation were detected for dose estimations for reference doses given in terms of absorbed dose to blood and for some participants, a laboratory-specific trend of systematic under- or overestimation was observed. The importance of regularly performed quality checks for a broad dose range became obvious to avoid misinterpretation of results.

• MeSH
• chromozomální aberace * účinky záření   MeSH
• dávka záření MeSH
• laboratoře normy   MeSH
• lidé MeSH
• radioizotopy kobaltu * MeSH
• radiometrie * metody   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.

• MeSH
• akutní myeloidní leukemie * terapie   genetika   mortalita   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   farmakologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• příprava pacienta k transplantaci * metody   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   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

The influence of t(v;22) sole, major route ACAs all (+8, n = 14; +Ph, n = 10; +19, n = 1), and -Y sole on progression-free survival. Survival curves are compared with those of patients with the standard t(9;22) translocation. Other ACAs or complex karyotypes did not influence survival.

• MeSH
• chromozomální aberace * MeSH
• chronická myeloidní leukemie * genetika   diagnóza   mortalita   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 22 genetika   MeSH
• lidské chromozomy, pár 9 genetika   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• senioři MeSH
• translokace genetická * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• dopisy MeSH