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1.
NPJ Precis Oncol ; 7(1): 96, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730754

RESUMO

The genomic spectrum of rhabdomyosarcoma (RMS) progression from primary to relapse is not fully understood. In this pilot study, we explore the sensitivity of various targeted and whole-genome NGS platforms in order to assess the best genomic approach of using liquid biopsy in future prospective clinical trials. Moreover, we investigate 35 paired primary/relapsed RMS from two contributing institutions, 18 fusion-positive (FP-RMS) and 17 fusion-negative RMS (FN-RMS) by either targeted DNA or whole exome sequencing (WES). In 10 cases, circulating tumor DNA (ctDNA) from multiple timepoints through clinical care and progression was analyzed for feasibility of liquid biopsy in monitoring treatment response/relapse. ctDNA alterations were evaluated using a targeted 36-gene custom RMS panel at high coverage for single-nucleotide variation and fusion detection, and a shallow whole-genome sequencing for copy number variation. FP-RMS have a stable genome with relapse, with common secondary alterations CDKN2A/B, MYCN, and CDK4 present at diagnosis and impacting survival. FP-RMS lacking major secondary events at baseline acquire recurrent MYCN and AKT1 alterations. FN-RMS acquire a higher number of new alterations, most commonly SMARCA2 missense mutations. ctDNA analyses detect pathognomonic variants in all RMS patients within our collection at diagnosis, regardless of type of alterations, and confirmed at relapse in 86% of FP-RMS and 100% FN-RMS. Moreover, a higher number of fusion reads is detected with increased disease burden and at relapse in patients following a fatal outcome. These results underscore patterns of tumor progression and provide rationale for using liquid biopsy to monitor treatment response.

2.
Am J Hum Genet ; 110(3): 427-441, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36787739

RESUMO

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation.


Assuntos
Neoplasias Ósseas , Sarcoma de Ewing , Humanos , Alelos , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia
3.
Cancers (Basel) ; 14(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35565244

RESUMO

BACKGROUND: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated. METHODS: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available. RESULTS: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification. CONCLUSION: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

4.
J Natl Cancer Inst ; 113(1): 80-87, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32239153

RESUMO

BACKGROUND: Uveal melanoma (UM) arises from malignant transformation of melanocytes in the uveal tract of the eye. This rare tumor has a poor outcome with frequent chemo-resistant liver metastases. BAP1 is the only known predisposing gene for UM. UMs are generally characterized by low tumor mutation burden, but some UMs display a high level of CpG>TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1093 primary UM case patients and a series of 192 UM tumors with monosomy 3 (M3). METHODS: We performed MBD4 targeted sequencing on pooled germline (n = 1093) and tumor (n = 192) DNA samples of UM patients. MBD4 variants (n = 28) were validated by Sanger sequencing. We performed whole-exome sequencing on available tumor samples harboring MBD4 variants (n = 9). Variants of unknown pathogenicity were further functionally assessed. RESULTS: We identified 8 deleterious MBD4 mutations in the consecutive UM series, a 9.15-fold (95% confidence interval = 4.24-fold to 19.73-fold) increased incidence compared with the general population (Fisher exact test, P = 2.00 × 10-5, 2-sided), and 4 additional deleterious MBD4 mutations in the M3 cohort, including 3 germline and 1 somatic mutations. Tumors carrying deleterious MBD4 mutations were all associated with high tumor mutation burden and a CpG>TpG hypermutator phenotype. CONCLUSIONS: We demonstrate that MBD4 is a new predisposing gene for UM associated with hypermutated M3 tumors. The tumor spectrum of this predisposing condition will likely expand with the addition of MBD4 to diagnostic panels. Tumors arising in such a context should be recognized because they may respond to immunotherapy.


Assuntos
Endodesoxirribonucleases/genética , Predisposição Genética para Doença , Melanoma/genética , Neoplasias Uveais/genética , Idoso , Feminino , Genótipo , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Fenótipo , Carga Tumoral/genética , Neoplasias Uveais/patologia , Sequenciamento do Exoma
5.
PLoS One ; 15(9): e0237792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881892

RESUMO

BACKGROUND: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. METHODS: We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). RESULTS: We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5×10-8) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84×10-8). CONCLUSIONS: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. IMPACT: Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Variação Genética , Células Germinativas/metabolismo , Sarcoma de Ewing/genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
6.
Nat Commun ; 9(1): 3184, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093639

RESUMO

Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk.


Assuntos
Perfilação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Sarcoma de Ewing/genética , Alelos , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Genótipo , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/genética , Humanos , Proteínas Nucleares , Proteínas de Fusão Oncogênica/genética , Polimorfismo de Nucleotídeo Único , Proteína Proto-Oncogênica c-fli-1/genética , Controle de Qualidade , Locos de Características Quantitativas , Proteína EWS de Ligação a RNA/genética , Risco , Sarcoma de Ewing/etnologia , Fatores de Transcrição/genética , População Branca , Proteínas de Peixe-Zebra
8.
Nat Genet ; 47(10): 1200-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26343384

RESUMO

While investigating cohorts of unclassified sarcomas by RNA sequencing, we identified 19 cases with inactivation of SMARCA4, which encodes an ATPase subunit of BAF chromatin-remodeling complexes. Clinically, the cases were all strikingly similar, presenting as compressive mediastino-pulmonary masses in 30- to 35-year-old adults with a median survival time of 7 months. To help define the nosological relationships of these tumors, we compared their transcriptomic profiles with those of SMARCA4-mutated small-cell carcinomas of the ovary, hypercalcemic type (SCCOHTs), SMARCB1-inactivated malignant rhabdoid tumors (MRTs) and lung carcinomas (of which 10% display SMARCA4 mutations). Gene profiling analyses demonstrated that these tumors were distinct from lung carcinomas but related to MRTs and SCCOHTs. Transcriptome analyses, further validated by immunohistochemistry, highlighted strong expression of SOX2, a marker that supports the differential diagnosis of these tumors from SMARCA4-deficient lung carcinomas. The prospective recruitment of cases confirmed this new category of 'SMARCA4-deficient thoracic sarcomas' as readily recognizable in clinical practice, providing opportunities to tailor their therapeutic management.


Assuntos
DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Sarcoma/genética , Neoplasias Torácicas/genética , Fatores de Transcrição/genética , Transcrição Gênica , Adulto , Humanos
9.
Cancer Res ; 72(17): 4494-503, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22930730

RESUMO

Ewing sarcoma is a rare but aggressive disease most common in young adults. This cancer is driven by a unique chimeric fusion oncogene but targeted strategies have been elusive. Here we report the identification of the protein kinase PKC-ß (PRKCB) as a disease-specific druggable target for treatment of Ewing sarcoma. We found that transcriptional activation of PRKCB was directly regulated by the chimeric fusion oncogene EWSR1-FLI1 that drives this cancer. PRKCB phosphorylated histone H3T6 to permit global maintenance of H3K4 trimethylation at a variety of gene promoters. PRKCB loss induced apoptosis in vitro and prevented tumor growth in vivo. Gene expression profiling revealed a strong overlap between genes modulated by EWSR1-FLI1 and PRKCB in regulating crucial signaling pathways. Taken together, our findings offer a preclinical proof-of-concept for PRKCB as a promising therapeutic target in Ewing sarcoma.


Assuntos
Proteínas de Ligação a Calmodulina/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Proteína Quinase C/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Animais , Proteínas de Ligação a Calmodulina/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Histonas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Nus , Camundongos SCID , Proteínas de Fusão Oncogênica/genética , Fosforilação , Proteína Quinase C/metabolismo , Proteína Quinase C beta , Proteína Proto-Oncogênica c-fli-1/genética , Interferência de RNA , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/genética
10.
Nat Genet ; 44(4): 461-6, 2012 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-22387997

RESUMO

The identification of subtype-specific translocations has revolutionized the diagnostics of sarcoma and has provided new insight into oncogenesis. We used RNA-seq to investigate samples from individuals diagnosed with small round cell tumors of bone, possibly Ewing sarcoma, but which lacked the canonical EWSR1-ETS translocation. A new fusion was observed between BCOR (encoding the BCL6 co-repressor) and CCNB3 (encoding the testis-specific cyclin B3) on the X chromosome. RNA-seq results were confirmed by RT-PCR and through cloning of the tumor-specific genomic translocation breakpoints. In total, 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcoma cases. Gene profiling experiments indicated that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly Ewing sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this subgroup of sarcoma and that overexpression of BCOR-CCNB3 or of truncated CCNB3 activates S phase in NIH3T3 cells. Thus, the intrachromosomal X-chromosome fusion described here represents a new subtype of bone sarcoma caused by a newly identified gene fusion mechanism.


Assuntos
Neoplasias Ósseas/genética , Ciclina B/genética , Fusão Gênica , Proteínas de Fusão Oncogênica/genética , Osteossarcoma/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Sarcoma/genética , Adolescente , Adulto , Animais , Sequência de Bases , Biomarcadores Tumorais/genética , Linhagem Celular , Criança , Cromossomos Humanos X/genética , Ciclina B/biossíntese , Ciclina B/metabolismo , Feminino , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Células NIH 3T3 , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteínas Repressoras/biossíntese , Proteínas Repressoras/metabolismo , Sarcoma/patologia , Sarcoma de Ewing/genética , Análise de Sequência de DNA , Translocação Genética , Adulto Jovem
11.
Nat Genet ; 44(3): 323-7, 2012 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-22327514

RESUMO

Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.


Assuntos
Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 1/genética , Proteínas de Ligação a DNA/genética , Proteína 2 de Resposta de Crescimento Precoce/genética , Predisposição Genética para Doença/genética , Sarcoma de Ewing/genética , França , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos/genética , Humanos , Modelos Logísticos , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único/genética , Sarcoma de Ewing/etnologia
12.
Diagn Cytopathol ; 40(1): 19-25, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22180234

RESUMO

Fine-needle aspiration (FNA) followed by a core-needle biopsy during general anesthesia is a method for diagnosing pediatric tumors in our Institute. To complete the diagnosis in the case of round cell sarcomas, cytology material is also used for genomic analyses, that is, karyotyping and molecular biology-derived techniques. Fifty primary Ewing sarcomas/peripheral neuroectodermal tumors (ES/PNET) in 50 patients were sampled. Cytological diagnoses were "malignant" in all cases and accurate (ES/PNET) in 46 (92%). Two (4%) cases were misdiagnosed as neuroblastoma, and two others (4%) as rhabdomyosarcoma and nephroblastoma. No suspicious or false-negative results were rendered. Karyotyping was performed in 20 (40%) cases and was interpretable in 17 cases but not in three cases. Molecular search for ES/PNET fusion transcripts were performed in all cases and were detected in 44 (88%) cases, but not in six (12%) cases. In conclusion, FNA assisted by genomic techniques is powerful methods to accurate diagnose ES/PNET.


Assuntos
Biópsia por Agulha Fina , Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico , Sarcoma de Ewing/diagnóstico , Cariótipo Anormal , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Tumores Neuroectodérmicos Primitivos Periféricos/genética , Reação em Cadeia da Polimerase em Tempo Real , Sarcoma de Ewing/genética , Adulto Jovem
13.
J Med Genet ; 47(12): 859-62, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20805368

RESUMO

BACKGROUND: Epidermal nevus (EN) is a congenital disorder characterised by hyperpigmented epidermal thickening following a Blaschko's line. It is due to somatic mutations in either FGFR3 or PIK3CA in half of the cases, and remains of unknown genetic origin in the other half. EN is also seen as part of complex developmental disorders or in association with bladder carcinomas, also related to FGFR3 and PIK3CA mutations. Mosaic mutations of these genes have been occasionally found in syndromic EN. CASE REPORT: The co-occurrence of EN, rhabdomyosarcoma, polycystic kidneys and growth retardation in an infant is described. RESULTS: An oncogenic G12D KRAS mutation was detected in both the epidermal component of the EN and in the rhabdomyosarcoma but not in the dermal component of the EN lesion or in unaffected tissues, including normal skin or blood. CONCLUSION: This report shows for the first time that a KRAS mutation in epiderma causes EN. Observation of the same G12D KRAS mutation in two distinct regions of the body strongly suggests a somatic mosaicism. Finally, this report highlights the potentially underestimated importance of mosaic oncogene mutations in childhood cancers.


Assuntos
Predisposição Genética para Doença , Mosaicismo , Mutação/genética , Doenças Renais Policísticas/genética , Proteínas Proto-Oncogênicas/genética , Rabdomiossarcoma/genética , Proteínas ras/genética , Substituição de Aminoácidos/genética , Sequência de Bases , Feminino , Dosagem de Genes/genética , Humanos , Lactente , Recém-Nascido , Dados de Sequência Molecular , Nevo Sebáceo de Jadassohn/complicações , Nevo Sebáceo de Jadassohn/genética , Nevo Sebáceo de Jadassohn/patologia , Fenótipo , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/patologia , Proteínas Proto-Oncogênicas p21(ras) , Rabdomiossarcoma/complicações , Rabdomiossarcoma/patologia
14.
J Clin Oncol ; 28(12): 1982-8, 2010 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-20308673

RESUMO

PURPOSE EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA architecture on disease progression and relapse was studied prospectively within the Euro-E.W.I.N.G. 99 clinical trial. PATIENTS AND METHODS Among 1,957 patients who registered before January 1, 2007, 703 primary tumors were accessible for the molecular biology study. Fusion type was assessed by polymerase chain reaction on frozen (n = 578) or paraffin-embedded materials (n = 125). The primary end point was the time to disease progression or relapse. Results After exclusion of noninformative patients, 565 patients were entered into the prognostic factor analysis comparing type 1 (n = 296), type 2 (n = 133), nontype 1/nontype 2 EWS-FLI1 (n = 91) and EWS-ERG fusions (n = 45). Median follow-up time was 4.5 years. The distribution of sex, age, tumor volume, tumor site, disease extension, or histologic response did not differ between the four fusion type groups. We did not observe any significant prognostic value of the fusion type on the risk of progression or relapse. The only slight difference was that the risk of progression or relapse associated with nontype 1/nontype 2 EWS-FLI1 fusions was 1.38 (95% CI, 0.96 to 2.0) times higher than risk associated with other fusion types, but it was not significant (P = .10). CONCLUSION In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions.


Assuntos
Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/genética , Proteína Proto-Oncogênica c-fli-1/genética , Sarcoma de Ewing/genética , Fatores de Transcrição/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Distribuição de Qui-Quadrado , Progressão da Doença , Europa (Continente) , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia , Inclusão em Parafina , Fenótipo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Proteína EWS de Ligação a RNA , Radioterapia Adjuvante , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Fatores de Risco , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/secundário , Sarcoma de Ewing/terapia , Transplante de Células-Tronco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Ann Diagn Pathol ; 14(1): 56-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20123459

RESUMO

A 39-year-old woman presented with an incidentally discovered mass of the left adrenal fossa. Computed tomography and magnetic resonance imaging did not show any other lesion. Histologically, this mass was composed of a dense proliferation of spindle cells with a fibrosarcomatous-like pattern. Immunohistochemistry using anticytokeratin showed some epithelial cells within the tumor. The diagnosis of primitive synovial sarcoma of the left adrenal fossa was confirmed by the presence of the characteristic t(X;18) translocation. Despite radiotherapy, several chemotherapies, and 2 other surgical resections, the patient died 30 months after the initial diagnosis. To our knowledge, this report constitutes the first described case of synovial sarcoma arising in the adrenal gland.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/patologia , Imageamento por Ressonância Magnética , Sarcoma Sinovial/patologia , Adulto , Biópsia , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica
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