Molecular Genetic Profiles Research Articles

Роль соматических мутаций в различных генах и проблема резистентности к ингибиторам тирозинкиназ у пациентов с хроническим миелолейкозом (обзор литературы)

The use of tyrosine kinase inhibitors (TKI) considerably improved the prognosis for most patients with chronic myeloid leukemia (CML). However, the issue of resistance to TKI therapy remains a challenge. At present, much attention is paid to the study of molecular genetic profile of tumor cells in CML patients and the role of somatic mutations in various genes, beyond BCR::ABL1, in the development of resistance to TKI therapy. New data emerge on the frequency of somatic mutations in various genes by the time of primary diagnosis of CML, commonly in the chronic phase, and on clonal changes during treatment, also when the disease progresses. Of particular interest is the role of somatic gene mutations in the transformation of CML into accelerated phase and blast crisis. Special importance is attributed to the time between the detection of somatic mutations and the registration of disease progression. This review focuses on the results of recent and most relevant studies of molecular genetic profile of CML patients at various disease stages. These studies aim to reveal the associations between somatic mutations in genes and a response to TKI therapy, as well as to assess the prognostic value of the mutations detected upon primary diagnosis and CML therapy. In future, this knowledge could be used in the clinic to optimize the therapy by decision making on the most effective TKIs and administering the targeted drugs aimed at alternative genetic abnormalities, as well as early allogeneic hematopoietic stem cell transplantation. The role of the most common somatic mutations in various genes, beyond BCR::ABL1, and the issues of disease resistance attract the attention of hematologists and basic scientists as a current and clinically relevant area of CML studies.

NTRK translocation: from general to specific

The molecular-genetic profile of lung cancer is highly diverse, complicating the formation of a unified patient portrait and necessitating the incorporation of specific genetic testing into diagnosis. There are key mechanisms for the activation of oncogenes, including point mutations, copy number changes (amplifications), and fusions, which are observed in non-small cell lung cancer (NSCLC). Modern molecular-targeted therapy for patients with NSCLC increases the duration of disease control and, in some cases, can transform a once-fatal disease into a chronic condition. Currently, the standard testing panel includes the identification of mutations in the EGFR gene (exons 18–21), ALK translocations, ROS1 translocations, and BRAF V600E mutations. However, less common alterations such as RET and NTRK translocations also occur. The use of next-generation sequencing (NGS) allows for the identification of rarer genetic alterations. NTRK gene fusions are considered oncogenic factors for various solid tumors in both adults and children. The prevalence of NTRK gene alterations varies by tumor type. However, in lung cancer, this type of genetic alteration is rare, with an overall prevalence of less than 3%, and typically the occurrence rate is less than 1%. Currently, three drugs have been included in international clinical guidelines as potential treatment options for NTRK translocations, demonstrating their effectiveness. Several other drugs are at various stages of clinical trials. In this review, we will highlight the existing data for a better understanding of the patient profile with NTRK and present a clinical case.

Role of Molecular-Genetic Profiling and Artificial Intelligence in Breast Cancer Diagnosis and insight into Targeted Pharmacotherapeutics

Breast cancer is a complex and diverse disease with varying responses to therapeutics. To address this diversity and offer personalized treatment plans, molecular and genetic analysis o breast tumors is crucial. The World Health Organization classifies breast cancer into different subtypes, including precursor lesions like Ductal carcinoma in-situ (DCIS), lobular carcinoma in-situ (LCIS), and Pleomorphic LCIS, which have the potential to develop into cancer. Invasive breast carcinomas infiltrate nearby tissues and can metastasize. These subtypes are categorized based on their microscopic appearances, such as Invasive Ductal Carcinoma (NOS), Invasive Lobular Carcinoma, Triple-Negative Breast Cancer (Estrogen receptor, Progesterone receptor, and, HER2), HER2-Positive Breast Cancer (HER2 overexpression), and less common types like Mucinous, Metaplastic, and Papillary carcinomas. Molecular and genetic profiling are powerful tools to aid in treatment decisions. Understanding the underlying biology of the disease helps physicians develop personalized treatment plans that consider the unique characteristics of each patient's tumor. Ongoing advancements in technology and research are improving our ability to diagnose and treat breast cancer effectively. This review presents an insight into molecular genetic profile, the role of artificial intelligence in breast cancer, and a concise overview of targeted pharmacotherapeutics for treating hormone receptor-based breast cancer.

Genetic Heterogeneity in Four Probands Reveals HGSNAT, KDM6B, LMNA and WFS1 Related Neurodevelopmental Disorders.

Background: Neurodevelopmental disorders of genetic etiology are a highly diverse set of congenital recurrent complications triggered by irregularities in the basic tenets of brain development. Methods: We present whole exome sequencing analysis and expression characteristics of the probands from four unrelated Pakistani consanguineous families with facial dysmorphism, neurodevelopmental, ophthalmic, auditory, verbal, psychiatric, behavioral, dental, and skeletal manifestations otherwise unexplained by clinical spectrum. Results: Whole exome sequencing identifies a novel, bi-allelic, missense variant in the HGSNAT gene [NM_152419.3: c.1411G > A (p. Glu471Lys) exon 14] for proband family E-1 and a rare, bi-allelic, non-frameshift variant in the KDM6B gene [NM_001348716.2: c.786_791dupACCACC (p. Pro263_Pro264dup) exon 10] for proband family E-2, and a novel, mono-allelic, missense variant in the LMNA gene [NM_170707.4: c. 1328 A > G (p. Glu443Gly) exon 8] for proband family E-3 and an ultra-rare, mono-allelic, missense variant in the WFS1 gene [NM_006005.3: c.2131G > A (p. Asp711Asn) exon 8] for proband family E-4. Protein modelling shows conformation and size modifications in mutated residues causing damage to the conserved domains expressed as neurocognitive pathology. Conclusions: The current study broadens the distinctly cultural and genetically inbred pool of the Pakistani population for harmful mutations, contributing to the ever-expanding phenotypic palette. The greatest aspirations are molecular genetic profiling and personalized treatment for individuals with complex neurological symptoms to improve their life activities.

Could SLC26A7 Be a Promising Marker for Preoperative Diagnosis of High-Grade Papillary Thyroid Carcinoma?

A modern classification distinguishes between two nosological entities posing an intermediate risk between differentiated and anaplastic carcinoma: poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma. There are currently few studies searching for the preoperative molecular genetic markers of high-grade papillary thyroid carcinoma (PTC HG), primarily because of a recent WHO reclassification and singling out of a separate entity: high-grade follicular cell-derived nonanaplastic thyroid carcinoma. Therefore, this work was aimed at identifying PTC HG-specific microRNAs and mRNAs that reliably distinguish them from differentiated papillary thyroid carcinoma in preoperative cytology specimens (fine-needle aspiration biopsies). A molecular genetic profile (expression levels of 14 genes and eight microRNAs) was studied in 110 cytology specimens from patients with PTC: 13 PTCs HG and 97 PTCs without features of HG. Of the examined eight microRNAs and 14 genes, significant differences in the expression levels between the PTC and PTC HG groups were revealed for genes SLC26A7, TFF3, and TPO. Only one gene (SLC26A7) proved to be crucial for detecting PTC HG. It showed the largest area under the ROC curve (0.816) in differentiation between the PTC and PTC HG groups and was the key element of the decision tree by ensuring 54% sensitivity and 87.6% specificity. Early preoperative diagnosis of PTC HG in patients with early stages of this cancer type will allow clinicians to modify a treatment strategy toward a larger surgery volume and lymph node dissection and may provide indications for subsequent radioactive iodine therapy.

Rapid intraoperative amplicon sequencing of CNS tumor markers

Currently, central nervous system tumors are diagnosed with an integrated diagnostic approach that combines histopathological examination with molecular genetic profiling, which requires days to weeks to achieve a precise and informative classification of CNS tumors. This study demonstrates the feasibility of rapid multiplex amplicon nanopore sequencing for identifying critical mutations relevant to molecular stratification of brain tumors within the timeframe of standard resection surgery. Utilizing live analysis of nanopore sequencing data, we evaluated the brain tumor-associated molecular markers IDH1 R132, IDH2 R172, pTERT C228 and C250, H3F3A K27 and G34, Hist1H3B K27, and BRAF V600. Our method achieved a turnaround time of 105 min at the point-of-care from receipt of a tumor biopsy to result with the potential to impact surgical strategy. Our approach can be integrated with recently developed DNA methylation-based diagnostic classification systems, corroborating diagnoses and even further specifying tumor grades, thus enabling a multimodal diagnostic intraoperative assessment of CNS malignancies.

VALIDATION OF 2HG-TARGETTED MR SPECTROSCOPY FOR IDENTIFYING IDH-MUTANT GLIOMAS

Abstract AIMS Diffuse gliomas, the most common adult primary brain tumour, are classified by their histological and molecular characteristics and genetic profile. Isocitrate dehydrogenase (IDH) mutant gliomas correlate with longer mean survival and progression-free survival time. In tumour cells, IDH mutations lead to metabolic changes and the production of oncometabolite 2-hydroxyglutarate (2HG). MR spectroscopy (MRS) can assess metabolic changes in disease states in-vivo and non-invasively. In this study, we demonstrate a validation pathway for two advanced MRS methods to be used as IDH-mutation biomarkers in clinic. METHOD Simulated, phantom, and healthy volunteer experiments were performed to optimise and validate three MRS sequences tuned for measuring 2HG. A PRESS sequence was used with TR/TE of 2500/97 ms aiming at the 2HG peaks around 2.25 ppm. An edited PRESS sequence, named MEGA-PRESS, tailored to 2HG 4.02 ppm peak was used with TR/TE of 3000/68 ms, 128 averages, and with editing pulses at 1.9 and 7.5 ppm. A long TE semi-LASER MRS sequence, with improved voxel localisation, was also used (TR/TE: 2500/110 ms). RESULTS Simulations were performed to find optimised sequence parameters and to develop basis sets for analysing the phantom and healthy volunteer acquisitions. Tumour-mimicking phantoms with variable concentrations of 2HG and cystathionine were created and validated with 800 MHz NMR spectroscopy. Phantoms were then used to assess the sensitivity and specificity of the MRS for 2HG and cystathionine. MEGA-PRESS proved Synthetic in-vivo 2HG spectra, combined from healthy volunteers and simulated or phantom-2HG spectra, were used to assess the spectral quality needed to reliably measure 2HG. CONCLUSION MEGA-PRESS proved to be the most robust MRS method and demonstrated accurate and precise measurement of phantom and synthetic 2HG with acceptable SNR. Clinical validation of the technique will need to be performed on LGG patient population, and the overall accuracy will be compared with patient IDH mutation status.

Molecular genetic and biochemical profiles of malignant neoplasms during pregnancy

The article presents a review of modern literature data on molecular-genetic and biochemical profiles of malignant tumors of varying locations. It is shown that molecular-genetic and transcription profiles of pregnancy-associated malignant tumors are systems consisting of various components, many of which remain poorly researched. Additionally, morphological and biochemical characteristics of the placenta and tumor tissue are discussed. In the recent years, individual researchers and research groups have demonstrated heightened interests in this problem which undoubtedly soon will lead to a deeper and stronger understanding of mechanisms of progression and metastasis of oncological diseases during pregnancy. The knowledge of the principles of normal embryogenesis as a process of intrauterine development of a fetus, as well as investigation of molecular basis of pathogenesis of spontaneous abortion will undoubtedly help in determination of new targets and development of new therapeutical molecules for cancer treatment.

Clinicopathological and molecular genetic insights into EBV-positive inflammatory follicular dendritic cell sarcoma

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV + IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. This study aimed to investigate the clinical characteristics, pathological features, and molecular genetic profiles of EBV + IFDCS to improve our understanding of these lesions. A total of 12 EBV + IFDCS specimens were obtained from patients in our pathology diagnostic center. The clinical data, morphology, immunohistochemistry, in situ hybridization, and high-throughput DNA-targeted sequencing data were collected, and follow-up data were analyzed. These data were compared with those of 6 patients with traditional FDCS. The patients with EBV + IFDCS ranged from 21 to 84 years old, with a mean age of 52.3 years and a male-to-female ratio of 1:5. At the last follow-up, all patients were alive, with 2 experiencing recurrence and metastasis. In these cases, four were classified as the classical subtype, four as the angiomatoid/sclerosing subtype, and four as the lymphoma-like subtype, with two cases also exhibiting epithelioid granulomas. All patients exhibited heterogeneous expression of follicular dendritic cell markers (CD21, CD23, CD35, and CXCL13) alongside the fibroblast marker SMA, with significantly higher expressions of IgG4, EBER, and SMA in EBV + IFDCS patients compared to FDCS patients (P < 0.05). Conversely, SSTR2, EGFR, and STAT3 expression were significantly lower in the EBV + IFDCS group (P < 0.05). The average value of EBER was significantly higher in the classical subtype group (P = 0.022). Among the four cases of EBV + IFDCS analyzed for molecular genetic features, one patient exhibited germline mutations in the CDKN1C, PDGFRA, MSH2, FANCG, MLH1, ALK, and RUNX1 genes; three exhibited simultaneous SNP variations in the MTHFR gene; and two exhibited simultaneous SNP variations in the NQO1 gene. We conducted KEGG pathway analysis on the mutant genes, revealing significant enrichment in the cAMP signaling pathway, which plays a crucial role in tumor development. Survival analysis demonstrated that the median PFS rates were not reached (NR) for EBV + IFDCS patients, compared to 5 months (HR = 7.76) for FDCS patients. The 3-year PFS rates were 66.67% and 16.67%, respectively. Compared with the FDCS group, EBV + IFDCS patients had a significantly longer median PFS time (p < 0.05). In conclusion, EBV + IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.

Angiosarcoma of the breast gland: molecular genetic profile, diagnosis and treatment

Angiosarcoma of the breast gland: molecular genetic profile, diagnosis and treatment

Molecular-genetic profile in patients with cardiomyopathy in Bulgaria

Molecular-genetic profile in patients with cardiomyopathy in Bulgaria

AML-379 Molecular-Genetic Profiling of NPM1-Mutated Acute Myeloid Leukemia and Its Prognostic Value

AML-379 Molecular-Genetic Profiling of NPM1-Mutated Acute Myeloid Leukemia and Its Prognostic Value

Insights into the Management of Chronic Myeloproliferative Neoplasms: Repercussions of the Age and Molecular-Genetic Profiles

Insights into the Management of Chronic Myeloproliferative Neoplasms: Repercussions of the Age and Molecular-Genetic Profiles

Molecular-Genetic Profiling of NPM1-Mutated Acute Myeloid Leukemia and Its Prognostic Value

Molecular-Genetic Profiling of NPM1-Mutated Acute Myeloid Leukemia and Its Prognostic Value

From Data Mining of Public Sources to Clinical Decision Support in Personalized Medicine.

Personalized medicine enables precise tumor treatment for a patient's molecular genetic profile. To devise optimal targeted treatment plans for patients in a molecular tumor board, physicians must consider alterations on gene- and proteins levels but also cancer cell phenotypes. Machine learning can uncover buried patterns, extract pivotal information, and unveil corresponding insights from available data. Publicly available datasets provide the amounts of data necessary. This work outlines the efficacy of various machine learning algorithms which could eventually serve as clinical decision support in a precision oncology setting. Leveraging algorithms including Random Forest, Decision tree, XGBoost, Logistic regression, Gaussian Naive Bayes, k nearest neighbor, and AdaBoost, we conducted two experiments for the breast invasive carcinoma dataset. Incorporated data includes patient-, molecular- and treatment data. The aim of the investigation was to predict medication treatment or type of treatment based on genetic profile. After preprocessing and application of ML algorithms, the first results were promising. Multiple factors challenge application in clinical care settings without carefully considering the limitations.

Health-Promoting Effects, Phytochemical Constituents and Molecular Genetic Profile of the Purple Carrot 'Purple Sun' (Daucus carota L.).

The purple carrot cultivar 'Purple Sun' (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12-14, 16, 17, 19, 22, and 23), anthocyanins (3-5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (-) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, 'Purple Sun' is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

A rare tumour – metastatic digital papillary adenocarcinoma: literature review, clinical case of successful therapy

Digital papillary adenocarcinoma (DPA ) is a rare malignant neoplasm of sweat glands, which was first described by Helwig in 1979 and then classified by Kao in 1987. This disease most often occurs in men aged 50–70 years and is characterized by a relatively favorable prognosis. In most cases, radical excision of the tumor leads to cure. However, 14–47 % of patients develop distant metastases with predominant lung involvement (70 %). The study of etiology and pathogenesis of this rare cancer and its molecular genetic profile seems to be interesting. Currently, there is no clear approach to the treatment of metastatic DPA , but sporadic cases of using chemotherapy have been reported. Aim of the study: to analyze current data on the pathogenesis of DPA , diagnostic features and treatment methods used, as well as to present the first clinical case of treatment of disseminated digital carcinoma with immune checkpoint inhibitors described in scientific literature. Material and Methods. A search of available literature published in Medline, Pubmed, etc. databases from 1984 to 2023 was performed, 21 sources were included in this review. Clinical Case Description. We present a rare case of metastatic digital papillary carcinoma in a 23-year-old male with disease manifestation at the age of 14 years. Lack of vigilance and awareness of oncologists and morphologists did not allow timely diagnosis of malignancy, even in case of 3 local recurrences of the disease. Only biopsy of a metastatic lung nodule with histological and IHC examination (of archival and new material) made it possible to make a correct diagnosis. This case revealed 2 potential targets that could be used for disease control: androgen receptor positive expression and PD -L1 expression with CPS =20. The use of immune response checkpoint inhibitors (ipilimumab + nivolumab) resulted in partial response followed by stable disease.

Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences.

The study aims to evaluate the clinical benefit of CGP in our Comprehensive Cancer Center Methods and patients: CGP was introduced into our routine clinical practice in 2021. An NGS-based large (> 500 genes) gene panel was used for cases where molecular genetic testing was approved by the National Molecular Tumor Board. From 2021 until August 2023 163 cases were tested. The majority of them were ECOG 0-1 patients with advanced-stage diseases, histologically rare cancer, or cancers with unknown primary tumours. Seventy-four cases (74 of 163, 45%) had clinically relevant genetic alterations. In 34 patients, the identified variants represented an indication for an approved therapy (approved by the Hungarian authorities, on-label indication), while in 40 cases the recommended therapy did not have an approved indication in Hungary for certain tumour types, but off-label indication could be recommended. Based on our CGP results, 24 patients (24/163; 14.7%) received targeted therapy. Treatment duration was between 1 and 60 months. In total 14 (14/163; 8.5% of the tested cases) patients had a positive clinical response (objective response or stable disease) and were treated for more than 16 weeks. NGS-based CGP was successfully introduced in our institution and a significant number of patients benefited from comprehensive genetic tests. Our preliminary results can serve as the starting point of Drug Rediscovery Protocol (DRUP) studies.

Non-Wilms renal tumors: Twenty years experience in a referral center

BackgroundNon-Wilms Renal Tumors (NWRT) constitute less than 10% of all renal tumors diagnosed in childhood. We studied our experience in the diagnosis and management of these tumors to compare our results with the current literature. Study designThis is a retrospective observational study which includes all patients aged 0-18 years with histopathological diagnosis of NWRT treated in our center during the period 2000-2022. ResultsWe identified 10 patients with diagnosis of: cystic nephroma(3), congenital mesoblastic nephroma(1), renal cell carcinoma(2), clear cell sarcoma of the kidney (2), renal Ewing's sarcoma(1) and malignant rhabdoid tumor of the kidney(1). Sixty percent (60%) were female. The median age at diagnosis was 3.25 years (IQR 1.5-10). Median age at diagnosis excluding CN was 6 years old (IQR 2.62-10.75). Molecular alterations were detected in 60% of the cases. Hematuria (40%) and palpable abdominal mass (40%) were the most frequent presenting symptoms. In total, 62.5% patients were misdiagnosed during the preoperative period as Wilms' tumor (WT), based on imaging data. A Radical nephroureterectomy was performed in all cases and staging lymphadenectomy in 70%. We recorded a major complication in one patient, who suffered a contralateral lower renal pole infarction due to section of a polar vessel during surgery. This patient had no preoperative vascular study. The recurrence-free survival rate was 90% with a median follow-up of 6.4 years (IQR 2-13.9). DiscussionRadiological imaging has fundamental importance in the diagnosis of renal tumors, especially to identify children who might benefit from initial surgical treatment or the indication of biopsy for preoperative histopathological confirmation before initiating cytotoxic treatment. However, there are no pathognomonic imaging findings that clearly differentiate between WT and other renal tumors, nor among the heterogeneous group of NWRT[3]. In our series, 62.5% of patients were misdiagnosed as WT based on imaging features.We found different molecular alterations in 60% of our patients (Table 1). None of them predispose to the development of bilateral tumors nor correlates with predisposing syndromes of metachronous tumors.Apart from its retrospective design, this study is limited by small number of cases and a long study period. ConclusionsCorrect differential diagnosis of NWRT is necessary for an adequate therapeutic approach. The molecular-genetic profile is an important step in the diagnosis of NWRT that allows for the use of targeted therapies in refractory patients. Detailed anatomical study by vascular mapping minimizes the risk of iatrogenic damage during tumor resection.