Wilms tumor (WT), the most common kidney neoplasm in children, is closely associated with hereditary factors. This study included 134 WT patients (62 males, median age of 7 years, age at diagnosis of 24.9 months) with unilateral (n = 90, 67%) or bilateral WT (n = 44, 33%). Genetic testing was performed using targeted sequencing of 415 genes and multiplex ligation-dependent probe amplification (MLPA). Twenty-five mutations in eight genes were found in 17% (n = 23) of patients: WT1 (n = 10), TRIM28 (n = 4), REST (n = 3), CHEK2 (n = 3), BRCA2 (n = 2), NF1 (n = 1), RAD50 (n = 1), and CDC73 (n = 1). Large deletions of the 11p13 region were revealed in 6% (n = 5) of patients. The 11p15 locus methylation was studied in blood, tumor, and healthy kidney tissue of nine patients suspected of Beckwith-Wiedemann syndrome (BWS) using methylation-sensitive MLPA (MS-MLPA). BWS was diagnosed in 3% (n = 4) of cases (one patient had mosaic disease). Thus, genetic and epigenetic aberrations were identified in 32 WT patients (24%). These patients had a higher frequency of bilateral WT and a higher rate of abnormalities compared to patients without aberrations (56% vs. 25%, p = 0.002; and 86% vs. 25%, p < 0.0001, respectively). The detection of WT hereditary predisposing factors is crucial for treatment strategies and long-term patient surveillance.

Mosaic RASopathies are rare conditions caused by postzygotic mutations in RAS/MAPK signaling pathway genes arising during embryonic development. They are mainly characterized by a combination of epidermal nevi with extra-cutaneous manifestations. Choosing between different entities can be challenging because of their substantial clinical and genetic overlap. Our aim was to demonstrate the importance of genetic background in accurate diagnosis and further prognostic assessment of disease progression by analyzing genotype–phenotype correlations within this clinical group. The study enrolled 18 patients (10 males, 8 females) aged from 1 month to 21 years with congenital nevi of craniofacial localization and variable extracutaneous abnormalities. DNA isolated from peripheral blood lymphocytes and affected tissues (nevus, tumor) was analyzed using a targeted next-generation sequencing (NGS) panel covering RAS/MAPK pathway genes, followed by Sanger sequencing. Eight patients were diagnosed with Schimmelpenning–Feuerstein–Mims syndrome caused by postzygotic mutations in the HRAS (n=4) or KRAS (n=4) genes. Seven patients were clinically diagnosed with phacomatosis pigmentokeratotica, and mosaic mutations were identified in the HRAS (n=4), KRAS (n=2), or BRAF (n=1) genes. Two patients with similar phenotypes carried somatic mutations in the PIK3CA and FGFR2 genes, respectively, and in one case no mutation was detected in the affected skin. We compared the spectrum of extracutaneous anomalies depending on the mutation in a specific gene by combining our data with data from other clinical cases of mosaic RASopathies described in the literature. In summary, 53 cases with HRAS postzygotic mutations and 41 cases with KRAS mutations were involved in the analysis of genotype–phenotype correlations. Hypophosphatemic rickets and malignant tumors were associated with mutations in the HRAS gene, while ophthalmological, neurological, cardiovascular, and renal disorders were more common in KRAS-mutant patients. Thus, genetic testing of affected tissue is essential for accurate diagnosis of these mosaic disorders. Taking into account clinical manifestations and the identified genotype–phenotype correlations may further assist in prognosis and patient management.

Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in the FANCA gene. At the age of 10, he received a bone marrow transplant from a compatible related donor. Conditioning therapy included busulfan, thymoglobulin, and fludarabine, while graft-versus-host disease (GvHD) prophylaxis was administered with rituximab, methotrexate, and cyclosporine A. Nevertheless, he developed chronic cutaneous GVHD, which was treated for four years with ruxolitinib and tacrolimus, achieving only partial control. During this period, locally advanced cutaneous SCC (T3N0M0, stage III) manifested on the face. Surgery, radiation therapy, and immunotherapy with pembrolizumab led only to an initial partial response. This first pediatric case of immunotherapy for SCC in FA highlights the challenges of treating this rare patient group. Nevertheless, combining radiation therapy with immunotherapy may represent a possible option for disease control.

Cancer predisposition syndromes (CPSs) account for 8.5-18% of all childhood cancer cases. Most of them are inherited in an autosomal dominant pattern; consequently, there is a 50% risk of transmission to offspring. Early detection of CPSs is crucial for choosing patient treatment strategies and for counseling in the family. This study enrolled 886 pediatric patients with hematologic and solid neoplasms from prospective and retrospective cohorts (2018-2025). Clinical exome or multigene panel sequencing was used to analyze blood DNA. Overall, 186 pathogenic/likely pathogenic (PLP) variants in cancer-associated genes were identified in 176/886 (20%) of patients, and the most frequently mutated were the NF1 (n = 35) and TP53 (n = 18) genes. Among the 186 PLP variants, 126/886 (14.2%) were causative for pediatric neoplasms, while 56/886 (6.3%) were heterozygous mutations associated with adult-onset CPSs affecting DNA repair. The highest total mutation rate was revealed in retinoblastoma (80%), peripheral nerve sheath tumors (60%), and pheochromocytoma/paraganglioma (47%), while the lowest rate was found in hematologic malignancies (4.6%) and neuroblastoma (12%). The wide range and high frequency of deleterious variants in pediatric patients, especially in those with solid tumors, highlights the importance of multigene panel sequencing for the accurate determination of CPSs.

Abstract Background Primary intracranial DICER1-mutant sarcomas (PIS-DICER1) are extremely rare and highly aggressive malignancies predominantly affecting pediatric patients. The presence of a DICER1 mutation defines a distinct biological subgroup, often associated with DICER1 syndrome – a hereditary tumor predisposition syndrome. Tumors located in the corpus callosum with invasion into the falx cerebri present a significant neurosurgical challenge due to their deep midline location and critical adjacent structures. Currently there is no standardized therapeutic approach for these rare tumors, making each case critical for understanding optimal management. Aim To present a challenging case of successfully treated primary intracranial DICER1-mutant sarcoma and the critical role of multimodal therapy, genetic confirmation and family screening within the framework of DICER1 tumor predisposition syndrome. Methods and Results Clinical presentation at age 6 included headache, dizziness and vomiting. Imaging revealed a large cystic-solid mass in the parietal lobe and corpus callosum. A partial resection of the right parietal tumor component was performed; however, gross total resection was unattainable due to invasion of the falx cerebrum and corpus callosum. Histopathology was consistent with a pleomorphic undifferentiated sarcoma. Given the patient’s age and tumor location, molecular profiling was recommended. Genetic analysis identified a previously unreported heterozygous DICER1variant (chr14:95111334, c.2239C>T, p.Gln747Ter). Parental testing was negative, confirming a de novo mutation. Following postoperative treatment with multi-agent chemotherapy (VAIA regimen) and proton beam radiotherapy, a complete radiographic response was achieved. This response has been maintained for 20 months since the end of therapy with no evidence of residual or recurrent disease. Conclusions Our experience suggests that multimodal regimen, including maximal safe cytoreduction, intensive polychemotherapy and radiotherapy can achieve durable remission for PIS-DICER1, even after non-radical surgery. It underscores the critical importance of a multidisciplinary approach in managing such rare and challenging tumors.

BackgroundGermline TP53 gene variants are intricately linked to Li-Fraumeni syndrome, a rare and aggressive hereditary cancer syndrome. This study investigated the frequency and spectrum of TP53 pathogenic variants associated with Li-Fraumeni syndrome in a large cohort of mainly breast cancer patients from Russia.MethodsThe study analyzed 3,455 genomic DNA samples from cancer patients using next-generation sequencing panels and whole-genome sequencing. Clinically significant TP53 variants were identified and validated using Sanger sequencing. The clinical and family history characteristics of patients with TP53 variants were analyzed.ResultsThe analysis identified 13 (0.4%) individuals with clinically significant germline TP53 variants, all of whom were females with either unilateral breast cancer or breast cancer as part of multiple primary malignant neoplasms. The average age of breast cancer manifestation was 39.9 years, with a median of 36 years. Only 38.5% of the TP53 mutation carriers met the modified Chompret criteria for TP53 testing.ConclusionsThe findings underscore the necessity of thorough phenotype and family history analysis in genetic counseling to effectively diagnose LFS, and emphasize the importance of identifying TP53 variant carriers for developing treatment strategies, prognosis, and monitoring, as well as for identifying high-risk family members. The study also highlights that the current guidelines fail to identify over half of the TP53 mutation carriers, suggesting the need for a more comprehensive approach to genetic testing in suspected hereditary cancer cases.

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90-100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS.

Background/objectivesSchimmelpenning-Feuerstein-Mims syndrome (SFMS) is a rare genodermatosis from the group of epidermal nevus syndromes with a wide range of clinical manifestations, including linear nevus sebaceous, ophthalmological disorders, cardiovascular abnormalities, nervous system and musculoskeletal system lesions. Benign and malignant neoplasms, precocious puberty, lymphedema and malformations of the lymphatic system may also be present. The main cause of the syndrome are postzygotic mutations in the RAS pathway, namely in the HRAS, KRAS, and NRAS genes. The aim of our work was to analyze previously described and genetically confirmed clinical cases of SFMS in order to reveal genotype-phenotype correlations.MethodsA systematic literature review (SLR) was conducted in several databases, including PubMed and ResearchGate to search for clinical cases of SFMS with genetic testing data from 1946 to 2025. The criterion for inclusion was considered to be the reference to SFMS or its synonyms in article titles with no limitations on language or date of publication. Also, no restrictions on patient age, ethnicity, presence/absence of photo-materials were applied. Only original articles reporting clinical case or case series with detection of postzygotic mutations in the HRAS, KRAS or NRAS genes were included.ResultsCurrently, 50 patients with SFMS and identified pathogenic variants in the HRAS (n = 17), KRAS (n = 30), or NRAS (n = 3) genes have been described in the literature. Analyzing presented phenotypic features of genetically confirmed cases of SFMS depending on the affected gene, we found that ophthalmological and central nervous system anomalities were more common for the KRAS-mut patients (p < 0.05). In contrast, patients with HRAS mutations were more likely to have skeletal abnormalities (p < 0.05). Benign and malignant tumors were diagnosed with equal frequency in both genetic groups, but renal tumors were strongly associated with KRAS mutations.ConclusionThe data obtained indicates the necessity of genetic testing for all patients suspected of SFMS to determine the individual risk of comorbidities and to form a personalized plan for dynamic follow-up.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251085872, identifier CRD420251085872.

Background Familial adenomatous polyposis (FAP) is a rare genetic disorder that is inherited in an autosomal dominant fashion. This disease is caused by a germline mutation in the APC gene, but in 20-30% of cases the disease occurs due to de novo mutations. There are several forms of the disease from severe, which is characterized by a pronounced number of polyps throughout the gastrointestinal tract (GIT) to a mild (attenuated) form of FAP, with less than 100 colonic polyps. According to various scientific literature, the risk of malignancy of epithelial formations reaches 100%. Identified epithelial formations of the gastrointestinal tract will lie down for endoscopic or surgical treatment. FAP is also characterized by neoplasms of extraintestinal localization, which characterizes it as a multisystem syndrome. There is a high risk of developing congenital retinal pigment epithelium hypertrophy, bone osteoma, fibroma, angiofibroma of the nose, thyroid carcinoma, hepatoblastoma, brain tumor and pancreatic tumor. Congenital retinal hypertrophy is the earliest extraintestinal manifestation of FAP. Thyroid cancer in young people, as a rule, is diagnosed first and serves as the basis for a comprehensive endoscopic diagnosis of the gastrointestinal tract. We present a rare case of FAP in a 14-year-old child associated with malignant neoplasms of extraintestinal localizations.

Gliomas are a heterogeneous group of brain tumors, among which the most aggressive subtype is glioblastoma, accounting for 60% of cases in adults. Available systemic treatment options are few and ineffective, so new approaches to therapies for glioblastoma are in high demand. In total, 131 patients with diffuse glioma were studied. Paired tumor–normal samples were sequenced on the Illumina platform; the panel included 812 genes associated with cancer development. Molecular profiles in clinically distinct groups were investigated. In low-grade glioma (LGG) patients (n = 18), the most common mutations were IDH1/2 (78%), ATRX (33%), TP53 (33%), PIK3CA (17%), and co-deletion 1p/19q (22%). In high-grade glioma (HGG) patients (n = 113), more frequently affected genes were CDKN2A/B (33%), TERTp (71%), PTEN (60%), TP53 (27%), and EGFR (40%). The independent predictors of better prognosis were tumor grade and IDH1/2 mutations. In IDH—wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS. Also, among genetic alterations, TERTp mutation and PTEN deletion were markers of poor prognosis. Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

This study evaluates the oncolytic potential of the Moscow strain of reovirus against human metastatic melanoma and glioblastoma cells. The Moscow strain effectively infects and replicates within human melanoma cell lines and primary glioblastoma cells, while sparing non-malignant human cells. Infection leads to the selective destruction of neoplastic cells, mediated by functional viral replication. A positive correlation was identified between viral RNA accumulation and tumor cell death, with no replication observed in non-malignant cells. This study highlights the critical roles of cathepsins B, L, and S as mediators of the oncolytic process. The pharmacological inhibition of these enzymes significantly attenuated reovirus-induced cytotoxicity in melanoma and glioblastoma cells. Conversely, PKR production analysis revealed minimal activation in reovirus-infected tumor cells, suggesting that the hyperactivation of the RAS-signaling pathway and subsequent PKR inhibition do not directly contribute to the selective efficacy of reovirus. Moreover, infected tumor cells exhibited features of both apoptotic and non-apoptotic death, emphasizing the intricate mechanisms of reovirus-mediated oncolysis. These findings underscore the therapeutic promise of the Moscow strain of reovirus as a selective and potent oncolytic agent for targeting melanoma and glioblastoma cells.

Objective: Identification of driver mutations in tumors is an extremely important task in oncology for the choice of treatment strategy and assessment of therapy efficacy. In many cases, especially in disease monitoring, there is a need to detect a small number of copies of the mutant allele against the background of excessive content of wild-type DNA. Methods: Genomic DNA was isolated from tumor tissue in paraffine blocks and amplified using polymerase-chain reaction (PCR) with blocking of wild-type DNA amplification via addition of locked-nucleic acid (LNA) oligonucleotides. Fluorescently labelled PCR-product enriched by IDH-mutant alleles was hybridized on a biochip with immobilized oligonucleotide probes which was able to determine 5 mutations in the IDH1 gene and 2 mutations in the IDH2 gene. Results and Discussion: The method was developed and tested on a collection of 26 samples of paraffinized tumor tissue (glioma, glioblastoma, chondrosarcoma). In three cases, R132C, R132L, and R132H mutations in the IDH1 gene were detected in tumor samples with low representation of the mutant allele. The limit of detection of mutant DNA was determined to be 0.1

Background. Cutis verticis gyrata is rare benign scalp disorder characterized by excessive skin and subcutaneous tissue proliferation and hypertrophy. Nowadays, there are three forms of this disease with various developmental mechanisms and associated manifestations. Clinical case description. This article presents the patient admitted with diagnosis and clinical picture of pachydermia, who underwent surgical excision of scalp abnormal tissues. However, the diagnosis of giant congenital melanocytic nevus was established according to the results of clinical examination. Later it was confirmed by histological and immunohistological studies. Moreover, pathogenic variants in the NRAS gene were not revealed. Conclusion. This case demonstrates the complexity of differential diagnosis of pachydermia that leads to careful examination of patients with morphogenetic studies of affected tissues samples.

Intracranial chondroid tumors are a heterogeneous group of neoplasms characterized by the presence of a cartilage matrix. These tumors exhibit overlapping clinical and histological features. Mutations in IDH1/2 genes serve as important diagnostic markers of tumor type, particularly chondrosarcoma. To improve the accuracy of IDH1/2 diagnostics, we compared three methods: biochip assay, real-time PCR with DNA melting analysis using TaqMan probes and sequencing (qPCR-DMA-Sanger), and immunohistochemistry (IHC). Tumor samples from 96 patients were investigated. The IDH1 mutations were detected in 34/64 (53%) chondrosarcomas; IHC detected 27/56 (48.2%) mutations, the qPCR-DMA-Sanger method 27/59 (46%) mutations, and the biochip assay revealed 29/60 (48.3%) mutations. The detection of IDH1 mutations in chordoma (2/15) and osteosarcoma (2/7) suggested the need for a revised diagnosis. In benign tumors, IDH1 mutations were present in chondroma (4/6), but absent in chondromyxoid fibroma (0/4). The most frequent IDH1 mutations were R132C (60%), R132L, and R132G (13.5% each), R132H (8%), and R132S (5%). The concordance between the biochip assay and IHC was 90%, between IHC and PCR-DMA-Sanger 83%, and between biochip assay and qPCR-DMA-Sanger was 98%, respectively. No IDH2 mutations were found. The use of independent diagnostic methods may improve the detection of IDH-mutant specimens in chondroid tumors.

Introduction. Epidermal growth factor receptor (EGFR) is a transmembrane protein of the receptor tyrosine kinase family that is activated in various cancers (non-small cell lung cancer, colorectal cancer, head and neck tumors). In glial brain tumors, increased EGFR expression levels are characteristic of the most aggressive subtype, glioblastoma. Frequent structural changes of EGFR in glioblastoma are amplification of the chromosome region where the EGFR gene is located, point mutations, as well as deletion of exons 2–7 of the EGFR gene leading to the formation of EGFRvIII transcript.Aim. To determine structural changes of the EGFR gene (point mutations and amplification of the EGFR gene, EGFRvIII transcript) in tumor samples using different methods and to evaluate their potential clinical significance.Materials and methods. The study included 75 patients with brain gliomas (70 of them glioblastoma) aged 34 to 78 years (mean age 56 years). DNA and RNA isolation was performed from fresh frozen tumor tissue, as well as from peripheral blood leukocytes. EGFR gene mutations were determined by next-generation sequencing (NGS), and β allele frequency (BAF) comparative analysis (normal-tumor) was performed to determine the copy number of chromosome 7 regions. Quantitative polymerase chain reaction was used to confirm the EGFR gene amplification in tumor samples, and reverse transcription-PCR was used to detect EGFRvIII variant.Results. The NGS method revealed 11/70 (16 %) mutations in coding regions of EGFR gene in glioblastoma samples, the EGFR gene amplification was detected in 26/70 (37 %) cases; no structural changes of the EGFR gene were detected in 5 glioma samples (astrocytoma, oligodendroglioma). All cases of EGFR gene amplification detected by NGS were confirmed by quantitative polymerase chain reaction. To search for EGFRvIII transcript, 31 tumor RNA samples were examined, of which EGFR amplification was present in 12 samples. EGFRvIII transcript was detected only in samples with EGFR gene amplification – 4/12 (33 %). To assess the clinical significance of structural gene alterations, the frequency of occurrence in primary and recurrent glioblastoma samples was compared.Conclusion. The NGS method allows to detect both point mutations and amplification of the EGFR gene. The EGFR gene amplification was associated with EGFRvIII mutation in 33 % of cases. No statistically significant differences in the frequency of structural changes in the EGFR gene between primary and relapsed glioblastomas were found.

Background/Objectives: Metastatic colorectal cancer remains a fatal disease, with a 5-year survival rate lower than 15%. The most common metastatic sites are the lungs and the liver, while skin metastases are very rare and often indicate a poor prognosis with a lower survival rate. Methods. Herein, we present the clinical case of a 62-year-old female patient with rectal cancer metastases to the skin of the anogenital and abdominal regions, diagnosed 2 years after completion of treatment of the underlying disease. Results: Histological examination of the skin lesions revealed adenocarcinoma, and expression of the same immunohistochemical markers was also found in the primary tumor and in the cutaneous metastases. However, next-generation sequencing demonstrated differences in the mutational profiles of the primary tumor and metastasis to the skin. Somatic mutations in the APC, TP53, and PTPN11 genes were revealed in primary rectal adenocarcinoma, but another pathogenic TP53 mutation and a frameshift variant in the DYNC1I1 gene were found in cutaneous metastases. The patient underwent several courses of FOLFOX6 chemotherapy in combination with bevacizumab, but the treatment was unsuccessful. An analysis of 50 clinical cases from the literature concerning various manifestations of cutaneous metastases of rectal cancer showed a median survival of 8.5 months from the time of detection of the skin lesions. Conclusions: In this regard, careful skin examination of patients with rectal cancer and timely detection of cutaneous metastases are essential steps in the follow-up of patients who have undergone treatment of the primary tumor.

Glioblastoma cell lines derived from different patients are widely used in tumor biology research and drug screening. A key feature of glioblastoma is the high level of inter- and intratumor heterogeneity that accounts for treatment resistance. Our aim was to investigate whether intratumor heterogeneity is maintained in cell models. Single-cell RNA sequencing was used to investigate the cellular composition of a tumor sample and six patient-derived glioblastoma cell lines. Three cell lines preserved the mutational profile of the original tumor, whereas three others differed from their precursors. Copy-number variation analysis showed significantly rearranged genomes in all the cell lines and in the tumor sample. The tumor had the most complex cell composition, including cancer cells and microenvironmental cells. Cell lines with a conserved genome had less diverse cellularity, and during cultivation, a relative increase in the stem-cell-derived progenitors was noticed. Cell lines with genomes different from those of the primary tumors mainly contained neural progenitor cells and microenvironmental cells. The establishment of cell lines without the driver mutations that are intrinsic to the original tumors may be related to the selection of clones or cell populations during cultivation. Thus, patient-derived glioblastoma cell lines differ substantially in their cellular profile, which should be taken into account in translational studies.

Assessments of breast cancer (BC) risk in carriers of pathogenic variants identified by gene panel testing in different populations are highly in demand worldwide. We performed target sequencing of 78 genes involved in DNA repair in 860 females with BC and 520 age- and family history-matched controls from Central Russia. Among BC patients, 562/860 (65.3%) were aged 50 years or less at the time of diagnosis. In total, 190/860 (22%) BC patients were carriers of 198 pathogenic/likely pathogenic (P/LP) variants in 30 genes, while among controls, 32/520 (6.2%) carriers of P/LP variants in 17 genes were identified. The odds ratio [95% confidence interval] was 16.3 [4.0-66.7] for BRCA1; 12.0 [2.9-45.9] for BRCA2; and 7.3 [0.9-56.7] for ATM (p < 0.05). Previously undescribed BRCA1/2, ATM, and PALB2 variants, as well as novel recurrent mutations, were identified. The contribution to BC susceptibility of truncating variants in the genes BARD1, RAD50, RAD51C, NBEAL1 (p. E1155*), and XRCC2 (p. P32fs) was evaluated. The BLM, NBN, and MUTYH genes did not demonstrate associations with BC risk. Finding deleterious mutations in BC patients is important for diagnosis and management; in controls, it opens up the possibility of prevention and early diagnostics.

Background. Proteus syndrome is extremely rare congenital multisystem disease with high variability in clinical manifestations. Its prevalence is unknown, there are less than 200 cases in the world literature. The syndrome is a classic example of somatic mosaicism, and all target drugs for its management are based on it. Clinical case description. This article describes two clinical cases with somatic variants of the nucleotide sequence in the AKT1 gene, mosaic form, revealed by the NGS method. Target drug (mTOR-inhibitors group) was assigned in one case. Conclusion. The description of the phenotypic features of patients with Proteus syndrome is crucial as this pathology is very rare. It is necessary to increase the awareness of clinicians about this disease to develop a plan for dynamic follow-up with consideration to life-threatening complications (malignant tumors and thrombembolia risk). Genetic verification of Proteus syndrome is mandatory nowadays as target therapy is actively developed and implemented, thus, revision of clinical guidelines is recommended.

Diagnosing skin diseases in children can be a complex interdisciplinary problem. Incontinentia pigmenti (IP), also known as Bloch-Sulzberger syndrome, is a rare hereditary genodermatosis related to a mutation in the IKBKG gene. We present a family case of IP described from the perspective of various specialists, including dermatologists, oncologists, geneticists, dentists, and trichologists. The peculiarity of this case is the development of squamous cell carcinoma (SCC) on the shin of a 10-year-old female patient with IP. The patient had a positive family history: her mother and two sisters also displayed clinical manifestations of IP with involvement of skin, teeth and hair. The presence of exons 4–10 deletion in the IKBKG gene in all affected females was confirmed by detailed genetic evaluation using long-range PCR, and also high degree of X-chromosome inactivation skewing was demonstrated. The family underwent a comprehensive examination and was followed up for 2 years with successful symptomatic treatment of dermatologic manifestations. Recommendations were also made regarding dental and hair problems. By the end of the follow-up period, patients had stabilized, with the exception of a 36-year-old mother who developed generalized morphea. The study demonstrates the varying expressiveness of clinical symptoms among family members and emphasizes the importance of timely diagnosis for effective management of patients with IP.