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1.
Rinsho Ketsueki ; 61(8): 874-878, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908049

RESUMO

A 74-year-old man was admitted to hospital due to suspected acute leukemia. He had a history of thymic carcinoma, which had been treated with carboplatin in combination with either paclitaxel or amrubicin. However, the tumor remained unresponsive to these treatments. Administration of tegafur/gimeracil/oteracil (TS-1) was initiated, which resulted in tumor size reduction and a partial response. However, leukopenia persisted after the last TS-1 treatment, and four years after the initial treatment, increased blast cell counts were found in a blood film . Bone marrow analysis showed blasts with Auer rods, faggot cells, and dysplastic promyelocytes. Flow cytometry was positive for CD13, CD33, CD34, CD117, and myeloperoxidase, but negative for HLA-DR. PML-RARA fluorescence in situ hybridization was positive. Cytogenetic analysis revealed 47,XY,t (15;17) (q22;q21),+21. Thus, therapy-related acute promyelocytic leukemia (tAPL) was diagnosed. The patient achieved and maintained complete remission for more than 20 months by a de novo APL-treatment regimen including all-trans retinoic acid, arsenic trioxide and tamibarotene. Moreover, the thymic carcinoma has remained stable. Although secondary malignancies of thymic carcinoma have been previously reported, therapy-related leukemia, especially tAPL, is very rare.


Assuntos
Leucemia Promielocítica Aguda , Timoma , Neoplasias do Timo , Idoso , Humanos , Hibridização in Situ Fluorescente , Masculino , Translocação Genética
2.
Ideggyogy Sz ; 73(7-08): 286-288, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32750246

RESUMO

Intracranial localization of Ewing's sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing's sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re-gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima-ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.


Assuntos
Encéfalo/diagnóstico por imagem , Sarcoma de Ewing/diagnóstico , Convulsões/etiologia , Vômito/etiologia , Neoplasias Ósseas/genética , Pré-Escolar , Craniotomia , Humanos , Hibridização in Situ Fluorescente , Pressão Intracraniana , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Qualidade de Vida , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/complicações , Sarcoma de Ewing/genética , Sarcoma de Ewing/cirurgia , Translocação Genética , Resultado do Tratamento
3.
Anticancer Res ; 40(8): 4373-4377, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727765

RESUMO

BACKGROUND: Giant cell tumor of tendon sheath (GCTTS) is a benign soft-tissue tumor that occurs predominantly in the fingers, with the capacity for local recurrence. The cytogenetic hallmark of GCTTS is the presence of 1p13 rearrangement. Several chromosomal segments have been recognized as translocation partners to 1p13. Herein, we describe a novel cytogenetic finding of GCTTS arising in the right thumb of a 71-year-old man. CASE REPORT: Physical examination revealed a 4-cm, elastic hard, immobile, nontender mass. Magnetic resonance imaging demonstrated a nodular mass with reduced signal intensity on both T1- and T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images showed intense heterogeneous enhancement of the mass. After a needle biopsy, complete excision was performed. Histologically, the tumor was composed of mononuclear cells admixed with multinucleated osteoclast-like giant cells, hemosiderin-laden macrophages, foamy cells, and inflammatory cells. Cytogenetic analysis revealed a reciprocal t(1;1)(p13;p34) translocation as the sole structural aberration. CONCLUSION: To the best of our knowledge, this is the first report of this tumor with t(1;1)(p13;p34).


Assuntos
Cromossomos Humanos Par 1 , Tumor de Células Gigantes de Bainha Tendinosa/genética , Translocação Genética , Idoso , Biópsia por Agulha , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico por imagem , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Humanos , Imagem por Ressonância Magnética , Masculino
4.
Nat Commun ; 11(1): 3390, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636395

RESUMO

Immunoglobulin (Ig) gene rearrangements and oncogenic translocations are routinely assessed during the characterization of B cell neoplasms and stratification of patients with distinct clinical and biological features, with the assessment done using Sanger sequencing, targeted next-generation sequencing, or fluorescence in situ hybridization (FISH). Currently, a complete Ig characterization cannot be extracted from whole-genome sequencing (WGS) data due to the inherent complexity of the Ig loci. Here, we introduce IgCaller, an algorithm designed to fully characterize Ig gene rearrangements and oncogenic translocations from short-read WGS data. Using a cohort of 404 patients comprising different subtypes of B cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements to provide additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic Ig translocations. Our data thus support IgCaller to be a reliable alternative to Sanger sequencing and FISH for studying the genetic properties of the Ig loci.


Assuntos
Genes de Imunoglobulinas , Hibridização in Situ Fluorescente/métodos , Oncogenes , Translocação Genética , Algoritmos , Estudos de Coortes , Genoma Humano , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Switching de Imunoglobulina , Linfoma de Células B/genética , Linfoma de Células B/imunologia , Software , Sequenciamento Completo do Genoma
5.
Nat Commun ; 11(1): 3339, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620764

RESUMO

Chromosomal NUP98-PHF23 translocation is associated with an aggressive form of acute myeloid leukemia (AML) and poor survival rate. Here, we report the molecular mechanisms by which NUP98-PHF23 recognizes the histone mark H3K4me3 and is inhibited by small molecule compounds, including disulfiram that directly targets the PHD finger of PHF23 (PHF23PHD). Our data support a critical role for the PHD fingers of NUP98-PHF23, and related NUP98-KDM5A and NUP98-BPTF fusions in driving leukemogenesis, and demonstrate that blocking this interaction in NUP98-PHF23 expressing AML cells leads to cell death through necrotic and late apoptosis pathways. An overlap of NUP98-KDM5A oncoprotein binding sites and H3K4me3-positive loci at the Hoxa/b gene clusters and Meis1 in ChIP-seq, together with NMR analysis of the H3K4me3-binding sites of the PHD fingers from PHF23, KDM5A and BPTF, suggests a common PHD finger-dependent mechanism that promotes leukemogenesis by this type of NUP98 fusions. Our findings highlight the direct correlation between the abilities of NUP98-PHD finger fusion chimeras to associate with H3K4me3-enriched chromatin and leukemic transformation.


Assuntos
Cromatina/metabolismo , Proteínas de Homeodomínio/metabolismo , Leucemia Mieloide/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Doença Aguda , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Cromatina/genética , Dissulfiram/farmacologia , Histonas/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Dedos de Zinco PHD/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteína 2 de Ligação ao Retinoblastoma/genética , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Translocação Genética/efeitos dos fármacos , Translocação Genética/genética
6.
Medicine (Baltimore) ; 99(26): e20894, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590798

RESUMO

RATIONALE: Couples with male balanced-translocation carriers may experience recurrent pregnancy loss (RPL). Although the expectant management of RPL has developed over many years, genetic counseling for RPL couples with male balanced-translocation carriers remains challenging. Here, we describe the expectant management of 2 male carriers of balanced translocations. PATIENT CONCERNS: A 32-year-old and a 28-year-old man presented at the clinic with diagnoses of infertility following spontaneous abortions by their wives. DIAGNOSIS: Both patients had normal semen diagnosed by routine semen analysis and underwent cytogenetic diagnoses. INTERVENTIONS: Following genetic counseling and informed consent, both couples voluntarily chose expectant management with natural conception. OUTCOMES: One couple experienced 2 natural pregnancies, the first of which ended in spontaneous abortion and the second produced a phenotypically normal infant. The other couple's first pregnancy resulted in a fetus with a balanced translocation confirmed by amniocentesis and cytogenetic analysis. LESSONS: Expectant management with natural conception may be an alternative to genetic counseling in male balanced-translocation carriers with RPL, especially those who are reluctant to undergo preimplantation diagnosis.


Assuntos
Infertilidade Masculina/genética , Resultado da Gravidez/genética , Translocação Genética/genética , Aborto Espontâneo/epidemiologia , Adulto , China/epidemiologia , Feminino , Humanos , Infertilidade Masculina/complicações , Infertilidade Masculina/epidemiologia , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Análise do Sêmen/métodos
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 983-988, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552969

RESUMO

OBJECTIVE: To study the potential significance and clinical application of FGFR1 gene abnormality in the diagnosis, clinical features, pathological mechanism and treatment in hematological tumors. METHODS: Clinical data of total of 29 patient with chromosome of 8 short arm (8P) abnormality who had more comprehensive medical history from 2013 to 2018 were collected. The karyotype analysis of bone marrow chromosomes in patients was carried out by using chromosome R band banding technique. FGFR1 gene was detected by using fluorescence in situ hybridization (FISH). RESULTS: Seven cases of FGFR1 gene abnormalities were decteted, including 3 cases of FGFR1 gene amplification, 2 cases of translocation, and 2 cases of deletion. Five patients with FGFR1 gene amplification or deletion not accompaned with eosinophilia, moreover the chromosome was a complex karyotype with poor prognosis; Two cases of FGFR1 gene translocation were non-complex chromosomal translocation and one of which survived for 6 years after bone marrow transplantation, the other chromosome karyotype showed no rearrangement of 8 short arm. However, FGFR1 gene rearrangement was confirmed by FISH analysis, which was a rare insertional translocation. CONCLUSION: FGFR1 gene amplification or deletion often occur in cases with complex karyotype, which not accompany eosinophilia, moreover have poor prognosis. The patients with FGFR1 gene translocation accompany eosinophilia which is consistent with the clinical characteristics of myeloid / lymphoid neoplasms with FGFR1 abnormality. Karyotype analysis combined with FISH method can improve the detection of abnormal clones.


Assuntos
Neoplasias Hematológicas/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Aberrações Cromossômicas , Neoplasias Hematológicas/metabolismo , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Translocação Genética
8.
Bull Cancer ; 107(7-8): 779-791, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32532420

RESUMO

Immunotherapy alone or in combination with chemotherapy is now an integral part of the treatment of metastatic NSCLC. This treatment is transforming the management of these cancers, with 20-30% of patients achieving long survival. However, disease progression under treatment is still the rule for the majority of patients, raising problems both in understanding its mechanisms and in subsequent appropriate management. This study examines current therapeutic options and proposes solutions to circumvent resistance to immunotherapy. The mechanisms of resistance to these treatments is also analysed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Quinase do Linfoma Anaplásico/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos Fase III como Assunto , Terapia Combinada/métodos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/fisiologia , Genes erbB-1 , Humanos , Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mutação , Receptores de Antígenos Quiméricos/uso terapêutico , Translocação Genética
10.
Proc Natl Acad Sci U S A ; 117(25): 14202-14208, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513722

RESUMO

FtsK protein contains a fast DNA motor that is involved in bacterial chromosome dimer resolution. During cell division, FtsK translocates double-stranded DNA until both dif recombination sites are placed at mid cell for subsequent dimer resolution. Here, we solved the 3.6-Å resolution electron cryo-microscopy structure of the motor domain of FtsK while translocating on its DNA substrate. Each subunit of the homo-hexameric ring adopts a unique conformation and one of three nucleotide states. Two DNA-binding loops within four subunits form a pair of spiral staircases within the ring, interacting with the two DNA strands. This suggests that simultaneous conformational changes in all ATPase domains at each catalytic step generate movement through a mechanism related to filament treadmilling. While the ring is only rotating around the DNA slowly, it is instead the conformational states that rotate around the ring as the DNA substrate is pushed through.


Assuntos
DNA Bacteriano/metabolismo , DNA/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Membrana/metabolismo , Translocação Genética/fisiologia , Divisão Celular/fisiologia , Segregação de Cromossomos , Cromossomos Bacterianos/metabolismo , Microscopia Crioeletrônica , DNA/química , DNA Bacteriano/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Moleculares , Conformação Proteica
11.
Cesk Patol ; 56(2): 89-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32493025

RESUMO

Dermatofibrosarcoma protuberans is a quite rare local aggressive tumor of dermis and subcutis, revealing characteristic morphology and chromosomal translocation (17; 22)(q21;q13) with gene fusion COL1A1-PDGFB. The tumour almost never metastasizes and complete excision signs an excellent prognosis. Approximately in 10% of cases, dermatofibrosarcoma undergoes a fibrosarcomatous transformation associated with metastatic disease and worse prognosis. In this paper, we refer a case of a male patient with subcutaneous tumor in back region, in which the small biopsy lead to diagnosis of a spindle cell sarcoma. However, only the histopathological examination of the entire tumor in the material from the radical surgery detected the dermatofibrosarcoma protuberans with fibrosarcomatous transformation. Both components of the tumor showed the characteristic genetic alteration. Identification of fibrosarcomatous component within the DFSP matters in prognosis. Distinction between fibrosarcoma arising within the dermatofibrosarcoma protuberans and fibrosarcoma arising de novo is of therapeutic consequence: the patients with metastatic or inoperable DFSP with fibrosarcomatous transformation may profit form imatinib treatment.


Assuntos
Dermatofibrossarcoma , Fibrossarcoma , Neoplasias Cutâneas , Dermatofibrossarcoma/tratamento farmacológico , Dermatofibrossarcoma/patologia , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Translocação Genética
13.
Cytogenet Genome Res ; 160(5): 255-263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544910

RESUMO

Fusions of the Runt-related transcription factor 1 (RUNX1) with different partner genes have been associated with various hematological disorders. Interestingly, the C-terminally truncated form of RUNX1 and RUNX1 fusion proteins are similarly considered important contributors to leukemogenesis. Here, we describe a 59-year-old male patient who was initially diagnosed with acute myeloid leukemia, inv(16)(p13;q22)/CBFB-MYH11 (FAB classification M4Eo). He achieved complete remission and negative CBFB-MYH11 status with daunorubicin/cytarabine combination chemotherapy but relapsed 3 years later. Cytogenetic analysis of relapsed leukemia cells revealed CBFB-MYH11 negativity and complex chromosomal abnormalities without inv(16)(p13;q22). RNA-seq identified the glutamate receptor, ionotropic, kinase 2 (GRIK2) gene on 6q16 as a novel fusion partner for RUNX1 in this case. Specifically, the fusion of RUNX1 to the GRIK2 antisense strand (RUNX1-GRIK2as) generated multiple missplicing transcripts. Because extremely low levels of wild-type GRIK2 were detected in leukemia cells, RUNX1-GRIK2as was thought to drive the pathogenesis associated with the RUNX1-GRIK2 fusion. The truncated RUNX1 generated from RUNX1-GRIK2as induced the expression of the granulocyte colony-stimulating factor (G-CSF) receptor on 32D myeloid leukemia cells and enhanced proliferation in response to G-CSF. In summary, the RUNX1-GRIK2as fusion emphasizes the importance of aberrantly truncated RUNX1 in leukemogenesis.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , DNA Antissenso/genética , Fusão Gênica/genética , Fator Estimulador de Colônias de Granulócitos/farmacologia , Leucemia Mieloide Aguda/genética , Receptores de Ácido Caínico/genética , Deleção de Sequência/genética , Translocação Genética/genética , Proliferação de Células/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores de Fator Estimulador de Colônias de Granulócitos/biossíntese , Receptores de Fator Estimulador de Colônias de Granulócitos/metabolismo
14.
Nat Cell Biol ; 22(7): 868-881, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483387

RESUMO

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a1-38) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a1-38 moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Translocação Genética , Proteínas rab de Ligação ao GTP/metabolismo , Adulto , Animais , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem , Proteínas rab de Ligação ao GTP/genética
15.
Cytogenet Genome Res ; 160(6): 321-328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32535594

RESUMO

Balanced chromosomal rearrangements are usually associated with a normal phenotype, although in some individuals, phenotypic alterations are observed. In these patients, molecular characterization of the breakpoints can reveal the pathogenic mechanism, providing the annotation of disease-associated loci and a better genotype-phenotype correlation. In this study, we describe a patient with a balanced reciprocal translocation between 4q27 and 7p22 associated with neurodevelopmental delay. We performed cytogenetic evaluation, next-generation sequencing of microdissected derivative chromosomes, and Sanger sequencing of the junction points to define the translocation's breakpoints at base pair resolution. We found that the PCDH10 and TNRC18 genes were disrupted by the breakpoints at chromosomes 4 and 7, respectively, with the formation of chimeric genes at the junction points. Gene expression studies in the patient's peripheral blood showed reduced expression of TNRC18, a gene with unknown function and clinical significance. PCDH10 plays a role in the development of the nervous system and might be involved with the patient's neurodevelopmental delay. In this study, the full molecular characterization of the junction points was shown as an efficient tool for fine breakpoint mapping in balanced translocations in order to unmask gene disruptions and investigate the potential pathogenic role of the disrupted genes.


Assuntos
Caderinas/genética , Pontos de Quebra do Cromossomo , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 7/genética , Transtornos do Neurodesenvolvimento/genética , Translocação Genética/genética , Adulto , Sequência de Bases , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Transtornos do Neurodesenvolvimento/psicologia
16.
Ann Hematol ; 99(7): 1561-1564, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451710

RESUMO

NUT midline carcinoma (NMC) is an aggressive neoplasm and mainly involved in the head and neck area. The defining genetic hallmark on these tumors is that testis-specific nuclear gene (NUTM1) fuses to bromodomain protein family member 4 gene (BRD4), resulting in the formation of BRD4-NUTM1 transcript. Here, we report a case with myeloid neoplasm complicating with eosinophilia (MLN-Eo) and rearrangement of PDGFRA, which co-exists with a new nucleosome assemble protein 1-like 4 gene (NAP1L4) NAP1L4-NUTM1 fusion. The patient have unusually clinical features and therapeutic reaction to imatinib mesylate. The cloned NAP1L4-NUTM1 gene structure is also determined.


Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 15/genética , Eosinofilia/genética , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Adulto , Eosinofilia/complicações , Eosinofilia/tratamento farmacológico , Humanos , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/patologia , Síndrome Hipereosinofílica/terapia , Mesilato de Imatinib/uso terapêutico , Leucemia/genética , Leucemia/patologia , Leucemia/terapia , Masculino , Mutação , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/isolamento & purificação , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Indução de Remissão , Translocação Genética/fisiologia
17.
Brain Tumor Pathol ; 37(3): 111-117, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32449046

RESUMO

The CIC-DUX4 translocation is the most common genetic alteration of small round cell sarcomas without EWSR1 rearrangement. These "Ewing-like sarcomas" usually occur in peripheral soft tissues, and rare primary central nervous system (CNS) tumors have been described. We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3-C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 10 months. Target RNA sequencing analysis revealed the CIC-DUX4 fusion gene. Methylation array analysis resulted in a diagnosis of "methylation class CNS Ewing sarcoma family tumor with CIC alteration". Although this tumor lacked characteristic histological features such as lobular structures in association with desmoplastic stroma, relatively uniform nuclei with prominent nucleoli and eosinophilic cytoplasm, which are often found in CIC-rearranged sarcomas of soft tissue, were identified. Recently, many CNS and soft tissue tumors require genetic analysis for precise diagnosis. To consider certain molecular testing, careful histological examination is essential.


Assuntos
Proteínas de Fusão Oncogênica/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/patologia , Translocação Genética , Diagnóstico Diferencial , Humanos , Imagem por Ressonância Magnética , Masculino , Sarcoma de Ewing/diagnóstico por imagem , Neoplasias de Tecidos Moles , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Adulto Jovem
18.
Cytogenet Genome Res ; 160(4): 177-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369810

RESUMO

Nonmosaic trisomy involving 19p13.3p13.2 is a very uncommon abnormality. At present, only 12 cases with this genetic condition have been reported in the literature. However, the size of the trisomic fragment is heterogeneous and thus, the clinical spectrum is variable. Herein, we report the clinical and cytogenetic characterization of a 5-year-old boy with nonmosaic trisomy 19p13.3p13.2 (7.38 Mb), generated by a derivative Y chromosome resulting from a de novo unbalanced translocation t(Y;19)(q12;p13.2). We demonstrated the integrity of the euchromatic regions in the abnormal Y chromosome to confirm the pure trisomy 19p. Our patient shares some clinical features described in other reported patients with pure trisomy 19p, such as craniofacial anomalies, developmental delay, and heart defects. Different to previous reports, our case exhibits frontal pachygyria and polymicrogyria. These additional features contribute to further delineate the clinical spectrum of trisomy 19p13.3p13.2.


Assuntos
Cromossomos Humanos Par 19/genética , Cromossomos Humanos Y/genética , Lisencefalia/genética , Polimicrogiria/genética , Translocação Genética/genética , Trissomia/genética , Pré-Escolar , Humanos , Lisencefalia/patologia , Masculino , Mosaicismo , Pais , Polimicrogiria/patologia , Trissomia/patologia , Adulto Jovem
19.
PLoS One ; 15(5): e0232592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365118

RESUMO

Chromosomal aberrations are relatively frequent pathologies in both humans and animals. Among them, translocations present a specific meiotic segregation pattern able to give a higher percentage of unbalanced gametes that can induce fertility problems. In this study, the meiotic segregation patterns of 1p, 1q and 18 Bubalus bubalis chromosomes were analyzed in both total sperm fraction and motile sperm fraction of a t(1p;18) carrier and a control bulls by triple-color FISH analysis with a pool of specific BAC probes. The frequencies of each total sperm fraction products in the carrier resulting from alternate, adjacent I, adjacent II and 3:1 segregation were 39%, 20%, 1% and 38%, respectively. On the other hand, the frequencies of each motile sperm fraction products in the carrier resulting from alternate, adjacent I, adjacent II and 3:1 segregation were 93%, 5%, 0% and 2%, respectively. The frequencies of normal sperms in the carrier were 27% and 69% in total sperm fraction and motile sperm fraction, respectively. The frequencies detected in motile sperm fraction were also validated by comparison with bull's progeny. To our knowledge, this is the first report on the meiotic segregation patterns in motile sperm fractions of B. bubalis bull carrying a chromosomal translocation. These data suggest that translocation has a very limited effect on aneuploidy in the gametes, and therefore, on the reproductive abilities of the bull.


Assuntos
Búfalos/genética , Meiose , Motilidade Espermática , Espermatozoides/fisiologia , Espermatozoides/ultraestrutura , Translocação Genética , Aneuploidia , Animais , Búfalos/fisiologia , Aberrações Cromossômicas , Segregação de Cromossomos , Cromossomos Artificiais Bacterianos , Criopreservação , Hibridização in Situ Fluorescente , Masculino , Reprodução
20.
BMC Med Genet ; 21(1): 101, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393201

RESUMO

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive, translocation-associated soft-tissue sarcoma that primarily affects children, adolescents, and young adults, with a striking male predominance. It is characterized by t(11;22) generating a novel EWSR1-WT1 fusion gene. Secondary genomic alterations are rarely described. METHODS: Tumor tissue from 83 DSRCT patients was assayed by hybrid-capture based comprehensive genomic profiling, FoundationOne® Heme next generation sequencing analysis of 406 genes and RNA sequencing of 265 genes. Tumor mutation burden was calculated from a minimum of 1.4 Mb sequenced DNA. Microsatellite instability status was determined by a novel algorithm analyzing 114 specific loci. RESULTS: Comprehensive genomic profiling identified several genomically-defined DSRCT subgroups. Recurrent genomic alterations were most frequently detected in FGFR4, ARID1A, TP53, MSH3, and MLL3 genes. With the exception of FGFR4, where the genomic alterations predicted activation, most of the alterations in the remaining genes predicted gene inactivation. No DSRCT were TMB or MSI high. CONCLUSIONS: In summary, recurrent secondary somatic alterations in FGFR4, ARID1A, TP53, MSH3, and MLL3 were detected in 82% of DSRCT, which is significantly greater than previously reported. These alterations may have both prognostic and therapeutic implications.


Assuntos
Biomarcadores Tumorais/genética , Tumor Desmoplásico de Pequenas Células Redondas/genética , Recidiva Local de Neoplasia/genética , Translocação Genética/genética , Adolescente , Adulto , Idoso , Criança , Aberrações Cromossômicas , Proteínas de Ligação a DNA/genética , Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Feminino , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 3 Homóloga a MutS/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/isolamento & purificação , Prognóstico , Proteína EWS de Ligação a RNA/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteínas WT1/genética , Adulto Jovem
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