Epithelial-myoepithelial carcinoma (EMC) can be a challenging diagnosis due to a lack of obvious invasion and bland cytology. We report an unusual case of a low-grade EMC with prominent fibrous stroma, an extensive solid-oncocytic differentiation and limited areas of morphological clearly identifiable characteristic biphasic (tubular) differentiation, clear cells and PAS-positive secretions/calcifications. Both areas were investigated by next generation sequencing (Oncomine comprehensive assay) and revealed a typical concordant HRAS p.Q61R mutation. An additional heterogeneous ARID1A (p.E672*) terminating mutation with loss of heterozygosity, which could be visualized predominantly in the solid-oncocytic differentiation by immunohistochemical loss of ARID1A protein expression, was found. This is the first case of an EMC of the salivary gland to be described with two separate tumor clones involving concordant HRAS and heterogeneous ARID1A mutations. The latter seem to be a "second hit" and was predominantly found in the solid-oncocytic differentiation, suggesting a potential morpho-molecular association.

• Klíčová slova
• ARID1A, Epithelial myoepithelial carcinoma, HRAS, Heterogeneous, Oncocytic, Salivary gland, Solid,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• karcinom genetika   patologie   MeSH
• lidé MeSH
• mutace MeSH
• myoepiteliální nádor genetika   patologie   MeSH
• nádory glandulární a epitelové genetika   patologie   MeSH
• nádory příušní žlázy genetika   patologie   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• ARID1A protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• HRAS protein, human MeSH Prohlížeč
• protoonkogenní proteiny p21(ras) MeSH
• transkripční faktory MeSH

Syringocystadenoma papilliferum (SCAP) is a benign tumor most commonly located on the head and neck area often associated with nevus sebaceus. In its usual location, the human papillomavirus (HPV) DNA and mutations in the RAS/mitogen-activated protein kinase signaling pathway have been detected in SCAP. We studied 16 cases of SCAP in the anogenital areas and buttock where this neoplasm is rare and attempted to find out whether SCAP in these sites have different histopathological and molecular biological features. It seems that there is no significant difference between the morphology of anogenital SCAP and SCAP in other locations. Several tumors in our cohort demonstrated features resembling those seen in warts, but HPV DNA was not found in these lesions. On the contrary, we identified DNA of HPV high-risk types in some tumors without HPV-related morphology. Our study confirms the role of HRAS and BRAF V600 mutations in the pathogenesis of SCAP, including SCAP in the anogenital areas and buttock.

• MeSH
• adenomy potních žláz genetika   patologie   virologie   MeSH
• anální kanál patologie   MeSH
• dospělí MeSH
• hýždě patologie   MeSH
• infekce papilomavirem epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• nádory mužských pohlavních orgánů genetika   patologie   MeSH
• nádory potních žláz genetika   patologie   virologie   MeSH
• nádory ženských pohlavních orgánů genetika   patologie   virologie   MeSH
• Papillomaviridae MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• HRAS protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf MeSH
• protoonkogenní proteiny p21(ras) MeSH

Myeloblastosis-associated virus 2 (MAV-2) is a highly tumorigenic simple avian retrovirus. Chickens infected in ovo with MAV-2 develop tumors in the kidneys, lungs, and liver with a short latency, less than 8 weeks. Here we report the results of molecular analyses of MAV-2-induced liver tumors that fall into three classes: hepatic hemangiosarcomas (HHSs), intrahepatic cholangiocarcinomas (ICCs), and hepatocellular carcinomas (HCCs). Comprehensive inverse PCR-based screening of 92 chicken liver tumors revealed that in ca. 86% of these tumors, MAV-2 provirus had integrated into one of four gene loci: HRAS, EGFR, MET, and RON Insertionally mutated genes correlated with tumor type: HRAS was hit in HHSs, MET in ICCs, RON mostly in ICCs, and EGFR mostly in HCCs. The provirus insertions led to the overexpression of the affected genes and, in the case of EGFR and RON, also to the truncation of exons encoding the extracellular ligand-binding domains of these transmembrane receptors. The structures of truncated EGFR and RON closely mimic the structures of oncogenic variants of these genes frequently found in human tumors (EGFRvIII and sfRON).IMPORTANCE These data describe the mechanisms of oncogenesis induced in chickens by the MAV-2 retrovirus. They also show that molecular processes converting cellular regulatory genes to cancer genes may be remarkably similar in chickens and humans. We suggest that the MAV-2 retrovirus-based model can complement experiments performed using mouse models and provide data that could translate to human medicine.

• Klíčová slova
• avian retroviruses, insertional mutagenesis, retroviral oncogenesis,
• MeSH
• cholangiokarcinom genetika   virologie   MeSH
• geny erbB-1 * MeSH
• hemangiosarkom genetika   virologie   MeSH
• hepatocelulární karcinom genetika   virologie   MeSH
• integrace viru MeSH
• inzerční mutageneze * MeSH
• karcinogeneze * MeSH
• kur domácí genetika   MeSH
• lidé MeSH
• nádory jater genetika   virologie   MeSH
• onkogeny MeSH
• protoonkogenní proteiny c-met genetika   MeSH
• proviry genetika   fyziologie   MeSH
• ptačí proteiny genetika   MeSH
• tyrosinkinasové receptory genetika   MeSH
• virus ptačí myeloblastózy genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protoonkogenní proteiny c-met MeSH
• ptačí proteiny MeSH
• RON protein MeSH Prohlížeč
• tyrosinkinasové receptory MeSH

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

• Klíčová slova
• ALK, Atypical Spitz tumor, BRAF –MAP3K8 fusion, HRAS mutation, MAP2K1 mutation, MET, NTRK1, NTRK2, NTRK3, RET, ROS1, Spitz melanoma, Spitz tumor, classification, dermoscopy-histopathology correlations, genetic alterations, histopathology, intermediate lesions, melanocytic lesions, melanocytomas, molecular driver, molecular morphological correlation, practical recommendations for diagnosis,
• MeSH
• epiteloidní a vřetenobuněčný névus * patologie   genetika   MeSH
• lidé MeSH
• melanom patologie   genetika   diagnóza   MeSH
• nádory kůže * patologie   genetika   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Mutations of the K-ras gene have been implicated in the pathogenesis of human lung adenocarcinomas. In most studies published so far, squamous cell lung cancers harbored ras mutations only exceptionally or no mutations were detected at all. We have examined 141 lung tumor DNA samples for mutations in codons 12, 13, and 61 of K-ras and H-ras oncogenes. A large panel of 118 squamous cell carcinomas was included in the study. For K-ras codon 12, we used a sensitive two-step PCR-restriction fragment length polymorphism method which detects <1% of mutated DNA in the sample. K-ras mutations were found in 17 tumors (12%; 14 in codon 12 and 3 in codon 13). Among 19 adenocarcinomas, mutation was revealed in 7 samples (37%). Of these, one sample harbored two point mutations in codon 12. Nine mutational events were found in squamous cell carcinomas (8%, one adenosquamous carcinoma included, all in codon 12). Of four large cell carcinomas, one contained a mutation. Mutant-enriched PCR products harboring mutations were directly sequenced. Fifteen mutational events were G-->T transversions or G-->A transitions, one was a G-->C transition, and one sample revealed a frameshift deletion of one G from codon 12. Similar mutational spectrum was found in both squamous cell carcinomas and adenocarcinomas, suggesting similar carcinogenic pathways in both histological types of the tumor. The presence of mutations did not correlate with the stage of the disease. Moreover, we analyzed all samples for mutations in codons 12, 13, and 61 of the H-ras gene. We found only one mutation in codon 12. Thus, H-ras mutations apparently play an inferior role in lung carcinogenesis. We conclude that mutations of the K-ras oncogene can play a role in the development of not only lung adenocarcinomas but also of a subset (about 8%) of squamous cell carcinomas.

• MeSH
• adenokarcinom genetika   MeSH
• adenoskvamózní karcinom genetika   MeSH
• bodová mutace * MeSH
• geny ras * MeSH
• kodon MeSH
• lidé MeSH
• nádory plic genetika   patologie   chirurgie   MeSH
• nemalobuněčný karcinom plic genetika   patologie   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus délky restrikčních fragmentů * MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• restrikční mapování MeSH
• sekvence nukleotidů MeSH
• spinocelulární karcinom genetika   patologie   chirurgie   MeSH
• substituce aminokyselin MeSH
• velkobuněčný karcinom genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HRAS protein, human MeSH Prohlížeč
• kodon MeSH
• protoonkogenní proteiny p21(ras) MeSH

We performed the genetic analysis of Rasopathy syndromes in patients from Central European by direct sequencing followed by next generation sequencing of genes associated with Rasopathies. All 51 patients harboured the typical features of Rasopathy syndromes. Thirty-five mutations were identified in the examined patients (22 in PTPN11, two in SOS1, one in RIT1, one in SHOC2, two in HRAS, three in BRAF, two in MAP2K1 and two in the NF1 gene). Two of them (p.Gly392Glu in the BRAF gene and p.Gln164Lys in the MAP2K1 gene) were novel with a potentially pathogenic effect on the structure of these proteins. Statistically significant differences in the presence of pulmonary stenosis (63.64% vs. 23.81%, P = 0.013897) and cryptorchidism (76.47% vs. 30%, P = 0.040224) were identified as the result of comparison of the prevalence of phenotypic features in patients with the phenotype of Noonan syndrome and mutation in the PTPN11 gene, with the prevalence of the same features in patients without PTPN11 mutation. Cryptorchidism as a statistically significant feature in our patients with PTPN11 mutation was not reported as significant in other European countries (Germany, Italy and Greece). The majority of mutations were clustered in exons 3 (45.45%), 8 (22.73%), and 13 (22.73%) of the PTPN11 gene.

• Klíčová slova
• BRAF, MAP2K1, PTPN11, Rasopathies, cardio-facio-cutaneous syndrome, central Europe, noonan syndrome,
• MeSH
• běloši genetika   MeSH
• dítě MeSH
• dospělí MeSH
• ektodermální dysplazie genetika   MeSH
• exony MeSH
• faciální stigmatizace MeSH
• fenotyp MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• kojenec MeSH
• kryptorchismus genetika   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutační analýza DNA * MeSH
• neprospívání genetika   MeSH
• Noonanové syndrom genetika   MeSH
• předškolní dítě MeSH
• protein SOS1 genetika   MeSH
• Ras proteiny genetika   MeSH
• stenóza pulmonální chlopně genetika   MeSH
• tyrosinfosfatasa nereceptorového typu 11 genetika   MeSH
• vrozené srdeční vady genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• intracelulární signální peptidy a proteiny MeSH
• protein SOS1 MeSH
• PTPN11 protein, human MeSH Prohlížeč
• Ras proteiny MeSH
• RIT1 protein, human MeSH Prohlížeč
• SHOC2 protein, human MeSH Prohlížeč
• tyrosinfosfatasa nereceptorového typu 11 MeSH

BACKGROUND: Increased frequency of chromosomal aberration in children of mothers aged 35 years and older is very well known and since 1973 it is an indication to investigate the foetal karyotype in cells obtained by invasive method (amniocentesis), because the genetic risk of severe affection is higher than the risk of necessary invasive method. Mutagenic effect of advanced paternal age is known only among geneticists (1-4). The reason is not only low absolute risk of new mutation but particularly a high number of involved genes and last not least the limited spectrum of autosomal dominant disorders without abiotrofic character. Therefore the preventive methods for elimination of this risk are very limited. Only a few of them could be recognized prenatally by noninvasive methods of prenatal diagnostics. METHODS: Genealogical, anamnestic and clinical data of 83 patients were studied with clinical suspection on neurocardiofaciocutaneous syndrome (NCFCs) (5-7). The diagnosis has not been confirmed in 29 patients, no mutation was detected in 8 investigated genes (PTPN11, SOS1, HRAS, BRAF, RAF1, MEK1, KRAS, NRAS). In 54 patients with autosomal dominant inherited Noonan syndrome, Costello syndrome and cardiofaciocutaneous syndrome the diagnosis was confirmed on DNA level and the biological fitness was estimated for each disorder. Paternal age at conception was compared in the group of patients with familial and sporadic occurrence of Noonan and NCFC syndromes. The clinical prognosis of this disorder is represented by biological fitness of patients. Coefficient of selection is 0,6 in Noonan and LEOPARD syndromes (29 from 48). All 6 patients with Costello and cardiofaciocutaneous syndromes developed due to a new mutation. CONCLUSION: Paternal age at birth was studied in 83 children patients with autosomal dominant Neurocardiofaciocutaneous syndrome (Noonan, LEOPARD, Costello, CFC) with a high population incidence and decreased biological fitness. Due to severe congenital heart defects, failure to thrive in infancy, increased risk for malignancy and further health problems the clinical prognosis of patients in the past was not good. Therefore high mutation rate is expected until now. Identification of genes responsible for manifestation of this disorder, enables to confirm the diagnosis and to recognize inherited and de novo mutations. Genealogy and DNA analysis of PTPN11, SOS1, HRAS, BRAF, RAF1, MEK1, KRAS and NRAS were obtained in cohort of 54 patients with NCFC syndromes and their parents. There were 48 patients with Noonan and LEOPARD syndromes, in 29 cases due to mutation de novo, 19 patients inherited the mutation from one of parents. All 6 patients with Costello syndrome and CFC syndrome were affected due to new mutation. DNA analysis revealed 32 mutations in PTPN11 gene, mutation in SOS1 gene was found in 10 patients, RAF1 mutation was present in 3 patients; mutation in MEK1, KRAS and NRAS genes was present in one patient each. In Costello syndrome and CFC syndrome mutations in HRAS (4 patients) and BRAF (2 patients) genes were detected. Genealogic data allow analysing parental age in the group of patients with new mutation and inherited mutation. Paternal age at conception of patients with Noonan syndrome due to new mutation was significantly increased in comparison to the group of fathers of Noonan patients with inherited mutation - 38,4 years and 29,6 years, resp., range 28 to 55 years and 25 to 35 years, resp. Maternal age was slightly increased too, -30,9 and 27,7, resp. and range 24 to 42 years and 21 to 36 years, resp. but not significantly. The results support the mutagenic effect of paternal age, espec. autosomal dominant mutations.

• MeSH
• chromozomální aberace MeSH
• dítě MeSH
• dominantní geny genetika   MeSH
• ektodermální dysplazie diagnóza   genetika   MeSH
• faciální stigmatizace MeSH
• genetická predispozice k nemoci genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutační analýza DNA * MeSH
• neprospívání diagnóza   genetika   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• prenatální diagnóza MeSH
• těhotenství MeSH
• věk otce * MeSH
• věkové faktory MeSH
• vrozené srdeční vady diagnóza   genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Salivary duct carcinoma (SDC) is one of the most aggressive salivary gland tumors, and prognosis remains poor for most patients. The aim of this study was to investigate the prognostic implications of biomarker immunoprofile in a cohort of SDC and to identify molecular characteristics through next-generation sequencing (NGS) in a subset of cases. Clinicopathological and follow-up information of 25 cases diagnosed as SDC was collected. Immunoexpression of AR, HER-2/neu, GATA3, CK5/6, and MIB1 was analyzed, and ERBB2 (HER-2/Neu) gene amplification was investigated by fluorescence in situ hybridization. Cases were classified under the "SDC revised classification system." Eight SDC cases were analyzed by targeted NGS for detection of gene fusions and variants. Overall survival and disease-free survival were analyzed with Kaplan-Meier curves and Cox regression. Most cases expressed AR (100%), GATA3 (73%), and CK5/6 (76.5%), and 42% expressed HER-2/neu. ERBB2 gene amplification was proven by fluorescence in situ hybridization in 7 of 15 (46%) cases. Apocrine HER2 (AR+/HER2+) subtype was significantly associated with lower overall survival (P = .05). NGS analysis revealed 9 pathogenic mutations in 7 SDC cases, and the most frequently mutated gene was HRAS (4/9) followed by PIK3CA (2/9) and TP53 (2/9). One case (1/9) presented homozygous deletion of locus 9p21 (CDKN2A), and another case (1/9) showed MDM2 amplification. In conclusion, we demonstrated that Apocrine HER2 (AR+/HER2+) is a potential biomarker of poor outcome in SDC. Furthermore, NGS analysis revealed recurrent mutations in SDC.

• Klíčová slova
• Immunoprofile, NGS, Prognosis, Salivary duct carcinoma, Salivary gland neoplasm,
• MeSH
• dospělí MeSH
• duktální karcinom diagnóza   patologie   MeSH
• homozygot MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace genetika   MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinných žláz diagnóza   genetika   patologie   MeSH
• sekvenční delece genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• vývody slinných žláz patologie   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
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH

Sclerosing polycystic adenoma (SPA) is a rare salivary gland neoplasm originally thought to represent a non-neoplastic lesion. Recently we have encountered an index case of apocrine intraductal carcinoma of parotid gland of 62-year-old man with invasive salivary duct carcinoma component arising from SPA, a combination of tumor entities that has never been published so far. Here, we further explore the nature of SPA by evaluating 36 cases that were identified from the authors' consultation files. The patients were 25 females and 11 males aged 11 to 79 years (mean, 47.8 y). All tumors originated from the parotid gland. Their size ranged from 11 to 70 mm (mean, 28 mm). Histologically, all cases revealed characteristic features of SPA, such as lobulated well-circumscribed growth, focal hyalinized sclerosis, presence of large acinar cells with abundant brightly eosinophilic intracytoplasmic granules, and ductal components with variable cytomorphologic characteristics, including foamy, vacuolated, apocrine, mucous, clear/ballooned, squamous, columnar and oncocyte-like cells. In all cases, there were foci of intraluminal solid and cribriform intercalated duct-like epithelial proliferations with variable dysplasia which were positive for S100 protein and SOX10, and fully enveloped by an intact layer of myoepithelial cells. In addition, 14/36 cases (39%) had focal intraductal cribriform and micropapillary apocrine-type dysplastic epithelial structures composed of cells positive for androgen receptors and negative for S100/SOX10. The intraductal proliferations of both types showed focal mild to severe dysplasia in 17 cases (17/36; 47%). Two cases showed overt malignant morphology ranging from high-grade intraductal carcinoma to invasive carcinoma with an apocrine ductal phenotype. Next generation sequencing using ArcherDX panel targeting RNA of 36 pan-cancer-related genes and/or a TruSight Oncology 170/500 Kit targeting a selection of DNA from 523 genes and RNA from 55 genes was performed. Tumor tissue was available for molecular analysis in 11 cases, and 9 (9/11; 82%) of them harbored genetic alterations in the PI3K pathway. Targeted sequencing revealed HRAS mutations c.37G>C, p.(Gly13Arg) (2 cases) and c.182A>G, p.(Gln61Arg) (2 cases), and PIK3CA mutations c.3140A>G, p.(His1047Arg) (3 cases), c.1633G>A, p.(Glu545Lys) (1 case), and c.1624G>A, p.(Glu542Lys) (1 case). Moreover, mutations in AKT1 c.49G>A, p.(Glu17Lys) and c.51dup, p.(Tyr18ValfsTer15); c.49_50delinsAG, p.(Glu17Arg) (as a double hit) were found (2 cases). In addition, germinal and somatic mutation of PTEN c.1003C>T, p.(Arg335Ter); c.445C>T, p.(Gln149Ter), respectively, were detected. Gene fusions were absent in all cases. These prevalent molecular alterations converging on one major cancer-related pathway support the notion that SPA is a true neoplasm with a significant potential to develop intraluminal epithelial proliferation with apocrine and/or intercalated duct-like phenotype. The name SPA more correctly reflects the true neoplastic nature of this enigmatic lesion.

• MeSH
• adenom enzymologie   genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• fosfatidylinositol-3-kinasy třídy I genetika   MeSH
• fosfohydroláza PTEN genetika   MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace * MeSH
• nádorové biomarkery analýza   genetika   MeSH
• nádory cystické, mucinózní a serózní enzymologie   genetika   patologie   MeSH
• nádory příušní žlázy enzymologie   genetika   patologie   MeSH
• protoonkogenní proteiny c-akt genetika   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři MeSH
• skleróza MeSH
• Check Tag
• dítě MeSH
• 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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AKT1 protein, human MeSH Prohlížeč
• fosfatidylinositol-3-kinasy třídy I MeSH
• fosfohydroláza PTEN MeSH
• HRAS protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• PIK3CA protein, human MeSH Prohlížeč
• protoonkogenní proteiny c-akt MeSH
• protoonkogenní proteiny p21(ras) MeSH
• PTEN protein, human MeSH Prohlížeč

Head and neck paragangliomas Paragangliomas and pheochromocytomas are rare, mostly benign neuroendocrine tumors, which are embryologically derived from neural crest cells of the autonomic nervous system. Paragangliomas are essentially the extra-adrenal counterparts of pheochromocytomas. As such this family of tumors can be subdivided into head and neck paragangliomas, pheochromocytomas and thoracic and abdominal extra-adrenal paragangliomas. Ten out of fifteen genes that contribute to the development of paragangliomas are more susceptible to the development of head and neck paragangliomas when mutated. Gene expression profiling revealed that pheochromocytomas and paragangliomas can be classified into two main clusters (C1 and C2) based on transcriptomes. These groups were defined according to their mutational status and as such strongly associated with specific tumorigenic pathways. The influence of the main genetic drivers on the somatic molecular phenotype was shown by DNA methylation and miRNA profiling. Certain subunits of succinate dehydrogenase (SDHx), von Hippel-Lindau (VHL) and transmembrane protein 127 (TMEM127) still have the highest impact on development of head and neck paragangliomas. The link between RAS proteins and the formation of pheochromocytoma and paragangliomas is clear due to the effect of receptor tyrosine-protein kinase (RET) and neurofibromatosis type 1 (NF1) in RAS signaling and recent discovery of the role of HRAS. The functions of MYC-associated factor X (MAX) and prolyl hydroxylase 2 (PHD2) mutations in the contribution to the pathogenesis of paragangliomas still remain unclear. Ongoing studies give us insight into the incidence of germline and somatic mutations, thus offering guidelines to early detection. Furthermore, these also show the risk of mistakenly assuming sporadic cases in the absence of definitive family history in head and neck paragangliomas.

• MeSH
• lidé MeSH
• mutace MeSH
• nádory hlavy a krku * genetika   MeSH
• paragangliom * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH