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1.
Zhonghua Bing Li Xue Za Zhi ; 49(1): 47-51, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31914534

RESUMO

Objective: To study the clinicopathological features, diagnostic features and differential diagnoses of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Six cases of SDSC diagnosed at Eye, Ear, Nose and Throat Hospital, Fudan University from 2016 to 2018 were retrieved; the clinical features, histomorphology, immunophenotype, radiology and outcome were analyzed with review of literature. Results: There were five men and one woman with age range of 37 years to 75 years (mean 56 years). One case was in stage T2, and 5 cases were in stage T4. Computer tomography and magnetic resonance imaging showed a mass occupying the sinonasal cavity with bone destruction in all six patients. Microscopically, the tumors had infiltrative margins. Four tumors were composed mostly of basaloid cells, which possessed high nuclear/cytoplasmic ratio,scant cytoplasm,and minimalnuclear pleomorphism; and the cells were arranged in sheets or nests in a desmoplastic stroma. Two tumors were composed of rhabdoid cells, which possessed abundant, eosinophilic cytoplasm and eccentric nuclei, often growing in a nests or sheets pattern. Immunohistochemical staining showed that 6/6 cases had complete loss of INI1, diffusely and strongly positive for CKpan, and were negative for S-100 and EBER ISH; 4/6 cases were focally positive for p63; 1/5 was focally positive for Syn and p16. The Ki-67 index was 30% to 70%. The follow-up period ranged 1-26 months, with one patient died of extensive metastases, one had local recurrence, and two had lymph node metastases; one was alive without disease, and one was lost to follow-up. Conclusions: SMARCB1 (INI1)-deficient sinonasal carcinoma is mostly aggressive, with rapid progression and poor prognosis. Histomorphological spectrum predominantly consists of basaloid type and rhabdoid type. The complete loss of nuclear expression of INI1 can help to distinguish this tumor from its many mimickers.


Assuntos
Neoplasias dos Seios Paranasais , Proteína SMARCB1/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Núcleo Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
2.
Autops. Case Rep ; 9(4): e2019120, Oct.-Dec. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024278

RESUMO

Chordoma is a rare tumor. It has unique clinical, pathological and immunohistochemical characteristics. Accurate diagnosis is essential as the tumor shows an aggressive clinical course and requires a multimodal therapeutic approach. A case with wide spread distant metastatic disease that was initially thought to represent metastatic thyroid carcinoma is presented. Appropriate clincopathologic correlation and the histologic findings raised the possibility of poorly differentiated chordoma. The diagnosis was confirmed by immunohistochemistry for INI-1 and Brachyury. The approach to the diagnosis emphasizing the clinical and pathologic findings of this case is discussed and reviewed in the context of the published literature.


Assuntos
Humanos , Masculino , Adulto , Cordoma/diagnóstico , Cordoma/patologia , Extremidade Superior , Proteína SMARCB1/uso terapêutico , Metástase Neoplásica , Notocorda/lesões
4.
Zhonghua Bing Li Xue Za Zhi ; 48(8): 590-595, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31422588

RESUMO

Objective: To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods: Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results: BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion: BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.


Assuntos
DNA Helicases/metabolismo , Neoplasias do Endométrio , Proteínas Nucleares/metabolismo , Proteína SMARCB1/metabolismo , Fatores de Transcrição/metabolismo , Biomarcadores Tumorais , China , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Imuno-Histoquímica
5.
BMC Cancer ; 19(1): 827, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438887

RESUMO

BACKGROUND: SMARCB1-deficient sinonasal carcinoma (SDSC) is an aggressive subtype of head and neck cancers that has a poor prognosis despite multimodal therapy. We present a unique case with next generation sequencing data of a patient who had SDSC with perineural invasion to the trigeminal nerve that progressed to a brain metastasis and eventually leptomeningeal spread. CASE PRESENTATION: A 42 year old female presented with facial pain and had resection of a tumor along the V2 division of the trigeminal nerve on the right. She underwent adjuvant stereotactic radiation. She developed further neurological symptoms and imaging demonstrated the tumor had infiltrated into the cavernous sinus as well as intradurally. She had surgical resection for removal of her brain metastasis and decompression of the cavernous sinus. Following her second surgery, she had adjuvant radiation and chemotherapy. Several months later she had quadriparesis and imaging was consistent with leptomeningeal spread. She underwent palliative radiation and ultimately transitioned quickly to comfort care and expired. Overall survival from time of diagnosis was 13 months. Next generation sequencing was carried out on her primary tumor and brain metastasis. The brain metastatic tissue had an increased tumor mutational burden in comparison to the primary. CONCLUSIONS: This is the first report of SDSC with perineural invasion progressing to leptomeningeal carcinomatosis. Continued next generation sequencing of the primary and metastatic tissue by clinicians is encouraged toprovide further insights into metastatic progression of rare solid tumors.


Assuntos
Carcinoma/etiologia , Carcinoma/patologia , Neoplasias dos Seios Paranasais/etiologia , Neoplasias dos Seios Paranasais/patologia , Proteína SMARCB1/deficiência , Adulto , Biomarcadores Tumorais , Carcinoma/diagnóstico por imagem , Progressão da Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Carcinomatose Meníngea/diagnóstico , Carcinomatose Meníngea/secundário , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único , Tomografia Computadorizada por Raios X
6.
Virchows Arch ; 475(4): 415-424, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444625

RESUMO

The molecular pathogenesis of esophageal carcinosarcoma (ECS) has not been fully investigated. This study includes 16 consequent cases of surgically resected ECS. Genetic alterations were independently examined for carcinoma in situ, carcinomatous, and sarcomatous areas. Six cases were analyzed by next-generation sequencing, and the remaining cases were analyzed by Sanger sequencing for TP53, PTEN, and INI1. Sarcomatous components in 3 cases showed histologically heterogenous feature of osteosarcoma. Lymph node metastasis was found in 12 out of 16 cases. Survival analysis revealed 5-year overall survival rate of 59.9%, and the median survival time was 5.37 years. TP53 was the most frequently mutated gene, being identified in 11 of 16 patients (68.8%), 7 of whom (63.6%) had the same mutations in both carcinomatous and sarcomatous areas. Almost complete concordance was found between p53 immunohistochemistry and TP53 missense mutations. Five-year overall survival tended to be worse for patients with p53 overexpression, although the data was not significant (p = 0.186). Nine of 16 patients (56.3%) showed loss of heterozygosity (LOH) at the INI1 locus, and this LOH status was consistent with both components. However, interestingly, INI1 expression was preserved in all cases. In addition, copy number variation analysis revealed gene amplification in several tyrosine kinase receptors. Accumulation of mutations in tumor suppressor genes such as TP53 and INI1 seemed to occur during ECS development.


Assuntos
Carcinossarcoma/genética , Carcinossarcoma/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/mortalidade , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína SMARCB1/genética , Proteína Supressora de Tumor p53/genética
7.
Nat Commun ; 10(1): 2966, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273213

RESUMO

Mutations in genes encoding components of BAF (BRG1/BRM-associated factor) chromatin remodeling complexes cause neurodevelopmental disorders and tumors. The mechanisms leading to the development of these two disease entities alone or in combination remain unclear. We generated mice with a heterozygous nervous system-specific partial loss-of-function mutation in a BAF core component gene, Smarcb1. These Smarcb1 mutant mice show various brain midline abnormalities that are also found in individuals with Coffin-Siris syndrome (CSS) caused by SMARCB1, SMARCE1, and ARID1B mutations and in SMARCB1-related intellectual disability (ID) with choroid plexus hyperplasia (CPH). Analyses of the Smarcb1 mutant animals indicate that one prominent midline abnormality, corpus callosum agenesis, is due to midline glia aberrations. Our results establish a novel role of Smarcb1 in the development of the brain midline and have important clinical implications for BAF complex-related ID/neurodevelopmental disorders.


Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Corpo Caloso/crescimento & desenvolvimento , Face/anormalidades , Deformidades Congênitas da Mão/genética , Deficiência Intelectual/genética , Micrognatismo/genética , Pescoço/anormalidades , Proteína SMARCB1/genética , Anormalidades Múltiplas/diagnóstico por imagem , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/patologia , Alelos , Animais , Criança , Pré-Escolar , Corpo Caloso/citologia , Corpo Caloso/diagnóstico por imagem , Modelos Animais de Doenças , Embrião de Mamíferos , Face/diagnóstico por imagem , Feminino , Deformidades Congênitas da Mão/diagnóstico por imagem , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Mutação com Perda de Função , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Transgênicos , Micrognatismo/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Neuroglia/patologia , Cultura Primária de Células
8.
Cancer Res ; 79(11): 2808-2809, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31160308

RESUMO

Malignant rhabdoid tumors (MRT) are rare but deadly pediatric tumors characterized by mutations in the SMARCB1/SNF5/INI1/BAF47 gene. Currently, there are no targeted therapies for MRTs. In a previous issue of Cancer Research, Howard and colleagues utilize the power of genome-wide RNAi and CRISPR screening to identify MDM2 and MDM4 as potential drug targets for MRTs. Most MRTs retain an intact p53 pathway and the authors show that these cells are particularly sensitive to MDM2 and MDM4 inhibition due to SMARCB1's role in regulating p53-depedent apoptotic genes. This discovery suggests potential clinical trials of MDM2 inhibitors in patients with MRT.See related article by Howard and colleagues; Cancer Res 79(9):2404-14.


Assuntos
Tumor Rabdoide/genética , Proteínas de Ciclo Celular , Criança , Proteínas Cromossômicas não Histona/genética , Humanos , Mutação , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína SMARCB1/genética
9.
World Neurosurg ; 128: 196-199, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082562

RESUMO

BACKGROUND: Atypical rhabdoid teratoid tumors are very rare embryonal tumors that typically affect children younger than 3 years old and are encountered intracranially. CASE DESCRIPTION: Here, we describe the case of a 19-year-old woman who presented with gait disturbances and coccydynia. Imaging revealed a cauda equina mass. The tumor was partially resected. Histology reported loss of SMARCB1/INI1 expression and therefore the diagnosis of atypical rhabdoid teratoid was established. The patient underwent radiation treatment, but within 3 months 2 relapses were manifested. CONCLUSIONS: Atypical rhabdoid teratoids are exceptionally rare in adults and are seldom found in spine; only 8 such cases have been reported in the medical literature. They are invariantly characterized by multiple relapses and dismal prognosis. The clinician must be attentive of leptomeningeal disseminations and 22q11 deletion-associated comorbidities.


Assuntos
Cauda Equina/diagnóstico por imagem , Neoplasias do Sistema Nervoso Periférico/diagnóstico por imagem , Tumor Rabdoide/diagnóstico por imagem , Teratoma/diagnóstico por imagem , Idade de Início , Cauda Equina/cirurgia , Feminino , Humanos , Laminectomia , Procedimentos Neurocirúrgicos , Neoplasias do Sistema Nervoso Periférico/metabolismo , Neoplasias do Sistema Nervoso Periférico/terapia , Radioterapia , Tumor Rabdoide/metabolismo , Tumor Rabdoide/terapia , Proteína SMARCB1/metabolismo , Teratoma/metabolismo , Teratoma/terapia , Adulto Jovem
10.
Nat Commun ; 10(1): 2014, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043611

RESUMO

SMARCB1 encodes the SNF5 subunit of the SWI/SNF chromatin remodeler. SNF5 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity. The concept that SNF5 is a coactivator for MYC, however, is at odds with its role as a tumor-suppressor, and with observations that loss of SNF5 leads to activation of MYC target genes. Here, we reexamine the relationship between MYC and SNF5 using biochemical and genome-wide approaches. We show that SNF5 inhibits the DNA-binding ability of MYC and impedes target gene recognition by MYC in cells. We further show that MYC regulation by SNF5 is separable from its role in chromatin remodeling, and that reintroduction of SNF5 into SMARCB1-null cells mimics the primary transcriptional effects of MYC inhibition. These observations reveal that SNF5 antagonizes MYC and provide a mechanism to explain how loss of SNF5 can drive malignancy.


Assuntos
Genes Supressores de Tumor , Proteínas Proto-Oncogênicas c-myc/genética , Tumor Rabdoide/genética , Proteína SMARCB1/metabolismo , Linhagem Celular Tumoral , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/genética , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Tumor Rabdoide/patologia , Proteína SMARCB1/genética
11.
Acta Cytol ; 63(5): 431-437, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31132763

RESUMO

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare entity within the subgroup of poorly differentiated sinonasal tract carcinomas. As there are only two papers describing the cytologic features of this entity, herein we describe the unique cytomorphologic features of a pulmonary metastasis of this tumor and include the differential diagnosis based on tumor location. The patient was a 53-year-old male who initially presented with sinus congestion and vision changes including left-eye proptosis and diplopia. The initial biopsy of the ethmoid-centered sinonasal mass was non-keratinizing squamous cell carcinoma based on strong immunoreactivity with p40 and absence of immunoreactivity for chromogranin, synaptophysin, p16, and EBER. However, the final diagnosis of the surgical resection was amended to SMARCB1 (INI-1)-deficient sinonasal carcinoma after additional immunohistochemical stains were performed. Post-primary resection, follow-up computed tomography imaging revealed significant interval progression of a solitary, initially indeterminate 1-cm lung nodule in the left upper lobe. Endobronchial ultrasound-guided fine-needle aspiration with concomitant core-needle biopsy was performed. Rapid on site evaluation of cytologic smears revealed a hypercellular specimen consisting of sheets of epithelioid cells with very scant to absent cytoplasm, ill-defined cell borders, enlarged fragile nuclei, and areas of nuclear molding. Mitotic figures were present. Other areas showed tumor cells with spindled to elongated nuclei and scant to ill-defined wispy cytoplasm. Both cytology cell block and core-needle biopsy histopathologic material showed the tumor cells to be negative for INI-1 nuclear staining as well as CK5/6, CAM5.2, p40, p63, CK7, AE1/3, and TTF-1. SMARCB1 (INI-1)-deficient sinonasal carcinoma can have a spectrum of morphologies and may mimic "small-round-blue-cell" and spindle-cell tumors on cytology preparations. Given the pulmonary location of the aspirate, familiarity with the cytomorphologic spectrum of SMARCB1 (INI-1)-deficient sinonasal carcinoma, inclusion of this entity within the differential diagnosis, and performance of immunohistochemistry will aid in arriving at the correct diagnosis.


Assuntos
Biomarcadores Tumorais/deficiência , Carcinoma/química , Carcinoma/secundário , Diferenciação Celular , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias dos Seios Paranasais/química , Neoplasias dos Seios Paranasais/patologia , Proteína SMARCB1/deficiência , Carcinoma/cirurgia , Diagnóstico Diferencial , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/cirurgia , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
12.
J Nippon Med Sch ; 86(2): 126-130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130564

RESUMO

Pseudomyogenic hemangioendothelioma (PMHE) is a new entity. It is an intermediate soft tissue tumor clinically and/or histopathologically mimicking some other high-grade malignant tumors and some inflammatory diseases. We report a case of PMHE on the left plantar surface of a 28-year-old woman. Histopathological examination of the resected specimen revealed spindle and epithelioid cells with plump and atypical nuclei proliferated in the dermis and subcutaneous fat tissue with marked fibroplasia. Both spindle and epithelioid cells had abundant eosinophilic cytoplasm. Neoplastic cells were diffusely positive for AE1/AE3, CK7, vimentin, CD31, FLI-1, ERG, and INI-1. From those findings, we made the diagnosis of PMHE. We describe the main points of differentiation between PMHE and diseases that have similar clinical and/or histopathological findings, including cellular dermatofibroma, spindle cell squamous cell carcinoma, epithelioid sarcoma, epithelioid hemangioendothelioma, epithelioid angiosarcoma, nodular or proliferative fasciitis, and granulomatous fibrosing granulation tissue due to a ruptured epidermal cyst.


Assuntos
Hemangioendotelioma Epitelioide/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Antiporters/metabolismo , Diagnóstico Diferencial , Feminino , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/genética , Humanos , Queratinas/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína SMARCB1/metabolismo , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Regulador Transcricional ERG/metabolismo , Vimentina/metabolismo
13.
Eur J Med Genet ; 62(8): 103680, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128261

RESUMO

Schwannomatosis is a rare affection predisposing to multiple peripheral neurologic tumors development. Approximatively, one third of patients with schwannomatosis are carriers of a germline mutation in LZTR1 (Leucin Zipper Transcription Regulator 1). Tumorigenesis in schwannomatosis responds to a somatic 5-hit/3-step mechanism resulting in a loss of function (LOF) of LZTR1 and the contiguous genes of locus 22q11.2q12.2. Effectively, LZTR1 is mapped on 22q11.2 and centromeric to SMARCB1 also implicated in the determinism of schwannomatosis and NF2, responsible for neurofibromatosis type 2. On a somatic point of view, LZTR1 mutations are known to drive with a significant frequency glioblastoma (GB) development. We report here two families in which segregate both multiple schwannomas and GB. In the first family, the proband received a diagnosis with of schwannomatosis after a surgery for a lumbar schwannoma at age 43, molecularly confirmed by identification of a germline heterozygous mutation in LZTR1. Her father, having unremarkable medical history deceased from an apparently isolated GB at age 59. In the second family, LZTR1-related schwannomatosis was diagnosed in the index case at age 70 after multiple schwannomas surgeries. Her elder sister had no neurological medical history before occurrence of a lethal GB at age 78. Molecular analysis of GB sample from both affected relatives showed the presence of the familial mutation. These observations hypothesize a potential link between schwannomatosis and the GB development.


Assuntos
Predisposição Genética para Doença , Glioblastoma/diagnóstico , Neurilemoma/diagnóstico , Neurofibromatoses/diagnóstico , Neoplasias Cutâneas/diagnóstico , Fatores de Transcrição/genética , Adulto , Idoso , Carcinogênese/genética , Feminino , Mutação em Linhagem Germinativa/genética , Glioblastoma/complicações , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Masculino , Neurilemoma/complicações , Neurilemoma/genética , Neurilemoma/patologia , Neurofibromatoses/complicações , Neurofibromatoses/genética , Neurofibromatoses/patologia , Linhagem , Proteína SMARCB1/genética , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
14.
World Neurosurg ; 127: 336-345, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004861

RESUMO

BACKGROUND: Adult sellar atypical teratoid/rhabdoid tumor (ATRT) is a rare diagnosis that has recently been shown to be a clinicopathologically and genetically distinct variant of ATRT occurring almost exclusively in middle-aged women. Although up to one third of pediatric ATRT is caused by a familial syndrome, no previous cases of a familial adult sellar ATRT have been reported. We present the first case report of a familial germline mutation causing adult sellar ATRT and a literature review of 29 previously reported cases of sporadic adult sellar ATRT. CASE DESCRIPTION: A 51-year-old woman with a family history of brain tumors spanning 3 generations presented with visual decline and was diagnosed with an adult sellar ATRT. Genetic studies showed a heterozygous splice-site loss-of-function mutation of the INI1 gene in exon 7. Treatment included endoscopic endonasal biopsy, craniospinal irradiation, and focal tumor boost, followed by adjuvant chemotherapy. CONCLUSIONS: This is the first case report of a familial germline mutation causing adult sellar ATRT. This article highlights the importance of a thorough family history and genetic testing in these individuals and reviews the current genetics, histopathology, and multidisciplinary treatment approach in this rare condition.


Assuntos
Neoplasias Encefálicas/genética , Mutação em Linhagem Germinativa/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Teratoma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
15.
Arkh Patol ; 81(2): 36-42, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31006778

RESUMO

The paper describes a clinical case of atypical teratoid/rhabdoid tumor with preserved INI1 expression and SMARCA4 gene mutations in an 8-month-old girl. Genome-wide DNA methylation, hierarchical clustering, and next-generation sequencing were used to make a tumor diagnosis. However, BRG1 immunohistochemical examination may be recommended in the routine practice of diagnosis and study of childhood CNS malignant tumors.


Assuntos
Neoplasias do Sistema Nervoso Central , Tumor Rabdoide , Proteína SMARCB1 , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Criança , Proteínas Cromossômicas não Histona , DNA Helicases/metabolismo , Feminino , Humanos , Lactente , Proteínas Nucleares/metabolismo , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genética , Proteína SMARCB1/metabolismo , Fatores de Transcrição/metabolismo
16.
Nat Commun ; 10(1): 1881, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015438

RESUMO

Bromodomain-containing protein 9 (BRD9) is a recently identified subunit of SWI/SNF(BAF) chromatin remodeling complexes, yet its function is poorly understood. Here, using a genome-wide CRISPR-Cas9 screen, we show that BRD9 is a specific vulnerability in pediatric malignant rhabdoid tumors (RTs), which are driven by inactivation of the SMARCB1 subunit of SWI/SNF. We find that BRD9 exists in a unique SWI/SNF sub-complex that lacks SMARCB1, which has been considered a core subunit. While SMARCB1-containing SWI/SNF complexes are bound preferentially at enhancers, we show that BRD9-containing complexes exist at both promoters and enhancers. Mechanistically, we show that SMARCB1 loss causes increased BRD9 incorporation into SWI/SNF thus providing insight into BRD9 vulnerability in RTs. Underlying the dependency, while its bromodomain is dispensable, the DUF3512 domain of BRD9 is essential for SWI/SNF integrity in the absence of SMARCB1. Collectively, our results reveal a BRD9-containing SWI/SNF subcomplex is required for the survival of SMARCB1-mutant RTs.


Assuntos
Montagem e Desmontagem da Cromatina , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Fatores de Transcrição/metabolismo , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Elementos Facilitadores Genéticos/genética , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Humanos , Mutação , Regiões Promotoras Genéticas/genética , Domínios Proteicos/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Tumor Rabdoide/patologia , Proteína SMARCB1/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética
17.
Ann Otol Rhinol Laryngol ; 128(7): 676-680, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30873845

RESUMO

OBJECTIVE: SMARCB1-deficient sinonasal tract carcinomas are an emerging subset of rare tumors recently described in the literature, with less than 100 reported cases. Given the aggressive nature of this tumor, timely diagnosis is especially important. We present a case report of a SMARCB1-deficient carcinoma of the sinonasal tract. METHODS: Case report with review of the literature. RESULTS: The patient was a 53-year-old male with computed tomography (CT)-proven mass of the right ethmoid and sphenoid sinuses. Rigid nasal endoscopy revealed a purple mass completely obstructing the right nasal cavity that extended inferiorly from the posterior ethmoids and sphenoid sinuses. Initial biopsy in the emergency room was nondiagnostic due to extensive tumor necrosis. Magnetic resonance imaging (MRI) revealed T2 hypointense enhancing mass centered in the right posterior ethmoids with invasion into the right orbital apex, classifying it as a T4b tumor. The patient underwent repeat biopsy with frozen section and tumor debulking. Immunohistochemical analysis of subsequent biopsy revealed complete loss of INI-1 and negative staining for other pertinent markers, alluding to the diagnosis of SMARCB1-deficient sinonasal tract carcinoma. CONCLUSION: Tumor necrosis may be problematic in obtaining a diagnosis for SMARCB1-deficient sinonasal carcinomas. Thus, sampling various regions of the tumor during initial biopsy can prevent delays in diagnosis and treatment.


Assuntos
Carcinoma/metabolismo , Seio Etmoidal/diagnóstico por imagem , Neoplasias dos Seios Paranasais/metabolismo , Proteína SMARCB1/metabolismo , Seio Esfenoidal/diagnóstico por imagem , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Carcinoma/cirurgia , Procedimentos Cirúrgicos de Citorredução , Seio Etmoidal/patologia , Seio Etmoidal/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Seio Esfenoidal/patologia , Seio Esfenoidal/cirurgia , Tomografia Computadorizada por Raios X
18.
Pathol Int ; 69(4): 241-245, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30843648

RESUMO

Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.


Assuntos
Carcinoma Medular/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Traço Falciforme/diagnóstico por imagem , Adulto , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Japão , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Proteína SMARCB1/metabolismo , Traço Falciforme/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
19.
Ophthalmic Plast Reconstr Surg ; 35(2): e41-e43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30856630

RESUMO

Integrase interactor 1 (INI1) is a tumor suppressor gene that is ubiquitously expressed in all nucleated cells. The loss of INI1 protein activity was first demonstrated in aggressive pediatric tumors, including atypical teratoid/rhabdoid (AT/RT) tumor of the central nervous system and malignant rhabdoid tumor of the kidney. Subsequently, INI1 deficiency was discovered in other pediatric and some adult neoplasms. The spectrum of INI1-negative tumors includes a wide variety of neoplasms that occur over a wide age range, are variably aggressive, and have a variable rhabdoid component on histopathologic evaluation. In this report, the authors describe a 27-year-old gravid woman with INI1-deficient carcinoma of the lacrimal gland, previously not described in this location.


Assuntos
Doenças do Aparelho Lacrimal/diagnóstico , Aparelho Lacrimal/diagnóstico por imagem , Complicações Neoplásicas na Gravidez , Tumor Rabdoide/diagnóstico , Proteína SMARCB1/deficiência , Adulto , Biomarcadores Tumorais/metabolismo , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Recém-Nascido , Doenças do Aparelho Lacrimal/metabolismo , Doenças do Aparelho Lacrimal/terapia , Gravidez , Tumor Rabdoide/metabolismo , Tumor Rabdoide/terapia , Tomografia Computadorizada por Raios X
20.
J Biol Chem ; 294(14): 5576-5589, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30745362

RESUMO

Histone deacetylase (HDAC) inhibitors (HDACis) have been widely tested in clinical trials for their ability to reverse HIV latency but have yielded only limited success. One HDACi, suberoylanilide hydroxamic acid (SAHA), exhibits off-target effects on host gene expression predicted to interfere with induction of HIV transcription. Romidepsin (RMD) has higher potency and specificity for class I HDACs implicated in maintaining HIV provirus in the latent state. More robust HIV reactivation has indeed been achieved with RMD use ex vivo than with SAHA; however, reduction of viral reservoir size has not been observed in clinical trials. Therefore, using RNA-Seq, we sought to compare the effects of SAHA and RMD on gene expression in primary CD4+ T cells. Among the genes whose expression was modulated by both HDACi agents, we identified genes previously implicated in HIV latency. Two genes, SMARCB1 and PARP1, whose modulation by SAHA and RMD is predicted to inhibit HIV reactivation, were evaluated in the major maturation subsets of CD4+ T cells and were consistently either up- or down-regulated by both HDACi compounds. Our results indicate that despite having different potencies and HDAC specificities, SAHA and RMD modulate an overlapping set of genes, implicated in HIV latency regulation. Some of these genes merit exploration as additional targets to improve the therapeutic outcomes of "shock and kill" strategies. The overall complexity of HDACi-induced responses among host genes with predicted stimulatory or inhibitory effects on HIV expression likely contributes to differential HDACi potencies and dictates the outcome of HIV reactivation.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Depsipeptídeos/farmacologia , HIV-1/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Ativação Viral/efeitos dos fármacos , Vorinostat/farmacologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Poli(ADP-Ribose) Polimerase-1/biossíntese , Proteína SMARCB1/biossíntese , Transcrição Genética/efeitos dos fármacos , Latência Viral/efeitos dos fármacos
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