Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Genes Chromosomes Cancer ; 60(10): 695-708, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34176176

RESUMO

Salivary gland tumors represent a diverse group of neoplasms that occasionally pose a diagnostic challenge for pathologists, particularly with limited sampling. Gene fusions, which may reflect genetic drivers, are increasingly recognized in a subset of these neoplasms, and can be leveraged for diagnostic purposes. We performed a retrospective analysis on a cohort of 80 benign and malignant salivary gland tumors, enriched for subtypes known to harbor recurrent fusion events, to validate the diagnostic use of a targeted RNA sequencing assay to detect fusion transcripts. Testing identified fusion genes in 71% (24/34) of pleomorphic adenoma and carcinoma-ex-pleomorphic adenoma, with 56% of cases showing rearrangement of PLAG1 and 15% HMGA2. In addition to confirming known partners for these genes, novel PLAG1 fusion partners were identified, including DSTN, NTF3, and MEG3; CNOT2 was identified as a novel fusion partner for HMGA2. In adenoid cystic carcinoma, 95% of cases (19/20) were positive for a fusion event. MYB was rearranged in 60% (12/20), MYBL1 in 30% (6/20), and NFIB in 5% (1/20); two tumors exhibited novel fusion products, including NFIB-TBPL1 and MYBL1-VCPIP1. Fusion genes were identified in 64% (9/14) of cases of mucoepidermoid carcinoma; MAML2 was confirmed to partner with either CRTC1 (43%) or CRTC3 (21%). One salivary duct carcinoma was found to harbor a novel RAPGEF6-ACSL6 fusion gene. Finally, as anticipated, gene fusions were not detected in any of the five acinic cell carcinomas included in the cohort. In summary, targeted RNA sequencing represents a diagnostically useful ancillary technique for identifying a variety of existing, and novel, fusion transcripts in the classification of salivary gland neoplasms.


Assuntos
Adenoma Pleomorfo/patologia , Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/genética , Neoplasias das Glândulas Salivares/patologia , Análise de Sequência de RNA/métodos , Adenoma Pleomorfo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/genética , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/genética , Adulto Jovem
2.
Genes Chromosomes Cancer ; 59(1): 23-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31433528

RESUMO

Alveolar soft part sarcoma (ASPS) is a rare malignancy that, since its initial description, remains a neoplasm of uncertain histogenesis. The disease-defining molecular event characterizing the diagnosis of ASPS is the ASPSCR1-TFE3 fusion gene. Following identification of an index case of ASPS with a novel TFE3 fusion partner, we performed a retrospective review to determine whether this represents an isolated event. We identified two additional cases, for a total of three cases lacking ASPSCR1 partners. The average patient age was 46 years (range, 17-65); two patients were female. The sites of origin included the transverse colon, foot, and dura. Each case exhibited a histomorphology typical of ASPS, and immunohistochemistry was positive for TFE3 in all cases. Routine molecular testing of the index patient demonstrated a HNRNPH3-TFE3 gene fusion; the remaining cases were found to have DVL2-TFE3 or PRCC-TFE3 fusion products. The latter two fusions have previously been identified in renal cell carcinoma; to our knowledge, this is the first report of a HNRNPH3-TFE3 gene fusion. These findings highlight a heretofore underrecognized genetic diversity in ASPS, which appears to more broadly molecularly overlap with that of translocation-associated renal cell carcinoma and PEComa. These results have immediate implications in the diagnosis of ASPS since assays reliant upon ASPSCR1 may yield a false negative result. While these findings further understanding of the molecular pathogenesis of ASPS, issues related to the histogenesis of this unusual neoplasm remain unresolved.

3.
J Pediatr Surg ; 50(3): 363-70, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25746690

RESUMO

BACKGROUND: Neonates with cholestasis may undergo many tests before biliary atresia (BA) or an alternative diagnosis is reached, and delayed intervention may worsen outcomes. An optimal diagnostic approach to reduce risk, cost, and delay has yet to be defined. The purpose of this study was to develop an algorithm that rapidly and accurately excludes BA for infants with cholestatic jaundice. METHODS: A single-center retrospective comparison of diagnostic workup was made between cholestatic infants with BA, and those without BA who underwent hepatobiliary iminodiacetic acid (HIDA) scan during admission. Patients were born between 2000 and 2010 and those older than 100days at assessment were excluded. Sensitivity and specificity analysis of predictive variables was performed and an algorithm constructed. RESULTS: There were 45 BA and 167 non-BA patients. Some variables were 100% sensitive for the exclusion of BA: conjugated bilirubin <2.5mg/dL, gamma-glutamyl transpeptidase <150U/L, excretion on HIDA, or a normal percutaneous cholangiogram. Clinical variables and ultrasound were less useful as screening tests owing to low specificity and sensitivity, respectively. Liver biopsy was 98% sensitive and 84% specific in the diagnosis of BA. An algorithm was constructed that rules out BA with a negative laparotomy rate of 3-22%. CONCLUSION: We propose a screening algorithm for infants with conjugated hyperbilirubinemia that permits efficient exclusion of BA with minimal invasive testing and with a low risk of negative laparotomy. This algorithm now requires prospective evaluation to determine its diagnostic accuracy and its ability to reduce hospital costs, patient morbidity, and time to Kasai portoenterostomy in patients with BA.


Assuntos
Algoritmos , Atresia Biliar/diagnóstico , Biópsia , Colangiografia/métodos , Icterícia Obstrutiva/diagnóstico , Laparotomia , Atresia Biliar/complicações , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Icterícia Obstrutiva/etiologia , Masculino , Estudos Retrospectivos
5.
J Clin Pathol ; 63(7): 630-4, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20591913

RESUMO

AIMS: To develop a fluorescence in-situ hybridisation (FISH) assay for detecting p16/CDKN2A deletion on paraffin tissue sections for use as an ancillary test to distinguish reactive from malignant mesothelial proliferations. METHOD: Dual-colour FISH for p16/CDKN2A and chromosome 9 (CEP-9) was performed on 11 benign mesothelial proliferations and 54 malignant pleural mesothelioma (MPM) cases to establish cut-off values for p16/CDKN2A deletion. A third MYC probe was used to verify cases showing homozygous deletion. Eight equivocal biopsies were used for assay testing. RESULTS: Cut-off values for p16/CDKN2A deletion were calculated based on FISH signalling patterns obtained from the benign controls (mean percent nuclei plus three standard deviations). Hemizygous deletion was defined as >44% of nuclei showing the hemizygous (one p16/CDKN2A, two CEP-9 signals) or >15% of nuclei showing the monosomy (one p16/CDKN2A, one CEP-9 signal) deletion patterns. None of the benign cases showed a homozygous deletion pattern (no p16/CDKN2A, at least one CEP-9 signal). In the malignant cases, the percentage of nuclei showing homozygous deletion ranged from 1% to 87%. Therefore, the cut-off value for homozygous deletion was defined as >10%. P16/CDKN2A deletion was detected in 61% (33/54) of MPM cases. Among the equivocal biopsies, four showed homozygous and one showed hemizygous p16/CDKN2A deletion. Age over 60 years, asbestos exposure and p16/CDKN2A deletion were associated with a worse prognosis. CONCLUSION: Distinction between benign and malignant mesothelial proliferations can be diagnostically challenging. FISH for p16/CDKN2A deletion is a useful test for confirming the diagnosis of MPM.


Assuntos
Deleção de Genes , Genes p16 , Hibridização in Situ Fluorescente/métodos , Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Amianto/efeitos adversos , Biópsia , Feminino , Humanos , Masculino , Mesotelioma/etiologia , Mesotelioma/genética , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Prognóstico , Estudos Prospectivos , Fumar/efeitos adversos , Análise de Sobrevida
6.
Arch Pathol Lab Med ; 132(8): 1342-5, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18684038

RESUMO

Precursor lymphoblastic lymphoma is an uncommon neoplasm. We report the case of a man who presented with precursor T lymphoblastic lymphoma and ultimately received an allogeneic bone marrow transplant from his human leukocyte antigen-identical sister. Four years later he developed recurrent disease. By means of DNA probing for the amelogenin locus and fluorescence in situ hybridization, the neoplastic cells of the recurrent lesion were found to be of donor origin. We offer the report of a patient with an unusual lymphoblastic lymphoma who, after successful bone marrow transplantation, developed the same disease of donor cell origin; further, we offer a literature review on donor cell lymphoma.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Neoplasias Renais/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Neoplasias Testiculares/cirurgia , Adulto , Amelogenina/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mapeamento Cromossômico , Evolução Fatal , Humanos , Hibridização in Situ Fluorescente , Neoplasias Renais/genética , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Irmãos , Neoplasias Testiculares/tratamento farmacológico , Doadores de Tecidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...