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1.
BMC Bioinformatics ; 21(1): 516, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176688

RESUMO

BACKGROUND: Reconstructing ancestral genomes is one of the central problems presented in genome rearrangement analysis since finding the most likely true ancestor is of significant importance in phylogenetic reconstruction. Large scale genome rearrangements can provide essential insights into evolutionary processes. However, when the genomes are large and distant, classical median solvers have failed to adequately address these challenges due to the exponential increase of the search space. Consequently, solving ancestral genome inference problems constitutes a task of paramount importance that continues to challenge the current methods used in this area, whose difficulty is further increased by the ongoing rapid accumulation of whole-genome data. RESULTS: In response to these challenges, we provide two contributions for ancestral genome inference. First, an improved discrete quantum-behaved particle swarm optimization algorithm (IDQPSO) by averaging two of the fitness values is proposed to address the discrete search space. Second, we incorporate DCJ sorting into the IDQPSO (IDQPSO-Median). In comparison with the other methods, when the genomes are large and distant, IDQPSO-Median has the lowest median score, the highest adjacency accuracy, and the closest distance to the true ancestor. In addition, we have integrated our IDQPSO-Median approach with the GRAPPA framework. Our experiments show that this new phylogenetic method is very accurate and effective by using IDQPSO-Median. CONCLUSIONS: Our experimental results demonstrate the advantages of IDQPSO-Median approach over the other methods when the genomes are large and distant. When our experimental results are evaluated in a comprehensive manner, it is clear that the IDQPSO-Median approach we propose achieves better scalability compared to existing algorithms. Moreover, our experimental results by using simulated and real datasets confirm that the IDQPSO-Median, when integrated with the GRAPPA framework, outperforms other heuristics in terms of accuracy, while also continuing to infer phylogenies that were equivalent or close to the true trees within 5 days of computation, which is far beyond the difficulty level that can be handled by GRAPPA.


Assuntos
Algoritmos , Genoma , Rearranjo Gênico
2.
Am J Clin Oncol ; 43(9): 670-675, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889839

RESUMO

During the course of therapy, patients with small cell lung cancer have been noted to develop transformation to non-small cell lung cancer and conversely, patients with non-small cell lung cancer have had transformation to small cell lung cancer or other non-small cell histologies. Transformation may occur after prior tyrosine kinase inhibitors, chemotherapy, immunotherapy or radiation therapy. These changes reflect on the overlapping biology of these cell types and the clinical need for re-biopsy at times of disease progression. The optimum therapy after transformation will depend upon prior therapies received, the functional capacity of the patient, and further research to define the best therapy options.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Transformação Celular Neoplásica , Receptores ErbB/genética , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Mutação , Nivolumabe/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1092-1096, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924108

RESUMO

OBJECTIVE: To analyze the laboratory and clinical features and prognosis of patients with acute lymphoblastic leukemia (ALL) and 11q23/MLL gene rearrangement. METHODS: A total of 725 patients with ALL were enrolled. The 11q23/MLL gene rearrangement and its partner genes were detected. The clinical and laboratory features and prognosis of patients with MLL gene rearrangement were analyzed. RESULTS: MLL gene rearrangement was detected in 42 cases (5.8%) of the patients, with the dominant immunophenotype being pro-B-ALL. Among the partner genes, the MLL/AF4 was the most common. Compared with the non-MLL/AF4 group, the MLL/AF4 group had higher white blood cell and immature cell counts. No significant difference was found in complete remission and 1-year overall survival (OS) rates between the two groups (P> 0.05). Compared with the non-MLL/AF4 group, the MLL/AF4 group had a higher recurrence rate (P<0.05) and a lower 3-year OS rate (P<0.05). Compared with the untransplantation group, the transplantation group had higher 2-year OS and progress free survival rates (P<0.05). Multivariate analysis suggested age ≤1 year, MLL/AF4 positive, early recurrence, and allogeneic hematopoietic stem cell transplant (Allo-HSCT) to be independent factors which can influence the survival of ALL patients with 11q23/MLL rearrangement (P<0.05). CONCLUSION: MLL/AF4 is the most common partner gene for 11q23/MLL gene rearrangement. This type of leukemia is mainly pro-B-ALL. Although conventional chemotherapy can achieve certain rate of remission, it is easy to relapse and the prognosis is very poor. Allo-HSCT may improve the prognosis.


Assuntos
Rearranjo Gênico , Transplante de Células-Tronco Hematopoéticas , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos
4.
J Cancer Res Ther ; 16(4): 850-854, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930129

RESUMO

Background: In non-small cell lung cancer common driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are usually mutually exclusive. This study aimed to elucidate the concurrence of EGFR mutation and ALK rearrangement in eastern India patients with primary lung adenocarcinoma and assess the response of EGFR tyrosine kinase inhibitor (TKI) therapy after 6 months in primary lung adenocarcinoma. Methods: We retrospectively analyzed 198 adenocarcinomas for EGFR and ALK mutations. EGFR and ALK tests were done by real-time polymerase chain reaction and immunohistochemistry (IHC) techniques, respectively. Radiological response was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1). Results: EGFR/ALK co-alteration was found in 4 adenocarcinoma patients. All were males with advanced disease. Younger patients had exon 19 deletion whereas older ones showed exon 21 mutation. The initial option of ALK-TKI in all four patients was excluded straightaway due to the high-cost burden of ALK-TKI. Two of them showed a partial response while other two had stable disease after 6 months of EGFR TKI therapy. Conclusion: EGFR/ALK co-alterations in adenocarcinomas albeit rare do exist. The challenge of monetary hurdle in developing countries with ALK TKI therapy can be handled by giving only EGFR TKI in these cases of concomitant mutations. Future perspective in research could be finding an agent with the potential of dual inhibition of ALK and EGFR.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Rearranjo Gênico , Neoplasias Pulmonares/genética , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Receptores ErbB/genética , Humanos , Índia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
6.
Proc Natl Acad Sci U S A ; 117(37): 22953-22961, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868446

RESUMO

The DNA-dependent protein kinase (DNA-PK), which is composed of the KU heterodimer and the large catalytic subunit (DNA-PKcs), is a classical nonhomologous end-joining (cNHEJ) factor. Naïve B cells undergo class switch recombination (CSR) to generate antibodies with different isotypes by joining two DNA double-strand breaks at different switching regions via the cNHEJ pathway. DNA-PK and the cNHEJ pathway play important roles in the DNA repair phase of CSR. To initiate cNHEJ, KU binds to DNA ends and recruits and activates DNA-PK. Activated DNA-PK phosphorylates DNA-PKcs at the S2056 and T2609 clusters. Loss of T2609 cluster phosphorylation increases radiation sensitivity but whether T2609 phosphorylation has a role in physiological DNA repair remains elusive. Using the DNA-PKcs 5A mouse model carrying alanine substitutions at the T2609 cluster, here we show that loss of T2609 phosphorylation of DNA-PKcs does not affect the CSR efficiency. Yet, the CSR junctions recovered from DNA-PKcs 5A/5A B cells reveal increased chromosomal translocations, extensive use of distal switch regions (consistent with end resection), and preferential usage of microhomology-all signs of the alternative end-joining pathway. Thus, these results uncover a role of DNA-PKcs T2609 phosphorylation in promoting cNHEJ repair pathway choice during CSR.


Assuntos
Proteína Quinase Ativada por DNA/genética , Proteína Quinase Ativada por DNA/metabolismo , Switching de Imunoglobulina/genética , Animais , Linfócitos B/imunologia , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Feminino , Rearranjo Gênico , Humanos , Switching de Imunoglobulina/fisiologia , Região de Troca de Imunoglobulinas/genética , Imunoglobulinas/genética , Autoantígeno Ku/metabolismo , Masculino , Camundongos , Camundongos da Linhagem 129 , Fosforilação , Recombinação Genética/genética , Translocação Genética
7.
Am J Surg Pathol ; 44(9): 1224-1234, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32804454

RESUMO

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody. These cancers harbored CAD-ALK (n=1), DIAPH2-ALK (n=2), EML4-ALK (n=2), LOC101929227-ALK (n=1), SLMAP-ALK (n=1), SPTBN1-ALK (n=4), and STRN-ALK (n=1) fusions, as detected by an RNA-based next-generation sequencing assay. ALK fusion carcinomas were diagnosed mostly in older patients with a 9:3 female predominance (median age: 72 y). All tumors, except a rectal one, occurred in the right colon. Most tumors were stage T3 (n=7) or T4 (n=3). Local lymph node and distant metastases were seen at presentation in 9 and 2 patients. These tumors showed moderate (n=6) or poor (n=3) glandular differentiation, solid medullary growth pattern (n=2), and pure mucinous morphology (n=1). DNA mismatch repair-deficient phenotype was identified in 10 cases. Tumor-infiltrating lymphocytes were prominent in 9 carcinomas. In 4 carcinomas, tumor cells showed strong, focal (n=3), or diffuse programmed death-ligand 1 immunoreactivity. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 tumors. Four patients died of disease within 3 years, and 7 were alive with follow-up ranging from 1 to 8 years. No mutations in BRAF, RAS, and in genes encoding components of PI3K-AKT/MTOR pathway were identified. However, 1 tumor had a loss-of-function PTEN mutation. Aberration of p53 signaling, TP53 mutations, and/or nuclear accumulation of p53 protein was seen in 9 cases. ALK fusion colorectal carcinomas are a distinct and rare subtype of colorectal cancers displaying some features of mismatch repair-deficient tumors.


Assuntos
Adenocarcinoma/genética , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Fusão Gênica , Rearranjo Gênico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Idoso , Biomarcadores Tumorais/análise , Neoplasias Colorretais/química , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Análise Mutacional de DNA , Europa (Continente) , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Japão , Metástase Linfática , Masculino , Mutação , Estadiamento de Neoplasias , Fenótipo , Resultado do Tratamento , Estados Unidos
8.
Arch Virol ; 165(10): 2355-2359, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748178

RESUMO

Two Staphylococcus aureus bacteriophages, KSAP7 and KSAP11, were isolated from sewage and characterized. Based on morphology and DNA sequences, they were assigned to the genus Silviavirus, subfamily Twortvirinae, family Herelleviridae, whose members are hypothesized to be suitable for bacteriophage therapy. The KSAP7 and KSAP11 genomes were 137,950 and 138,307 bp in size, respectively. Although their DNA sequences were almost identical, evidence of site-specific DNA rearrangements was found in two regions. Changes in the number of PIEPEK amino acid sequence repeats encoded by orf10 and the insertion/deletion of a 541-bp sequence that includes a possible tail-related gene were identified.


Assuntos
Caudovirales/genética , DNA Viral/genética , Genoma Viral , Filogenia , Fagos de Staphylococcus/genética , Staphylococcus aureus/virologia , Sequência de Aminoácidos , Caudovirales/classificação , Caudovirales/isolamento & purificação , Rearranjo Gênico , Tamanho do Genoma , Mutação INDEL , Japão , Fases de Leitura Aberta , Terapia por Fagos , Alinhamento de Sequência , Fagos de Staphylococcus/classificação , Fagos de Staphylococcus/isolamento & purificação
10.
PLoS Biol ; 18(8): e3000756, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745139

RESUMO

Recognition of self and nonself is important for outcrossing organisms, and different mating types establish the barrier against self-mating. In the unicellular ciliate T. thermophila, mating type determination requires complex DNA rearrangements at a single mat locus during conjugation to produce a type-specific gene pair (MTA and MTB) for 1 of 7 possible mating types. Surprisingly, we found that decreased expression of the DNA breakage-repair protein Ku80 at late stages of conjugation generated persistent selfing phenotype in the progeny. DNA analysis revealed multiple mating-type gene pairs as well as a variety of mis-paired, unusually arranged mating-type genes in these selfers that resemble some proposed rearrangement intermediates. They are found also in normal cells during conjugation and are lost after 10 fissions but are retained in Ku mutants. Silencing of TKU80 or TKU70-2 immediately after conjugation also generated selfing phenotype, revealing a hidden DNA rearrangement process beyond conjugation. Mating reactions between the mutant and normal cells suggest a 2-component system for self-nonself-recognition through MTA and MTB genes.


Assuntos
DNA de Protozoário/genética , Rearranjo Gênico , Autoantígeno Ku/genética , Proteínas de Protozoários/genética , Tetrahymena thermophila/genética , Conjugação Genética , Cruzamentos Genéticos , DNA de Protozoário/metabolismo , Expressão Gênica , Inativação Gênica , Autoantígeno Ku/metabolismo , Fenótipo , Proteínas de Protozoários/metabolismo , Reprodução , Tetrahymena thermophila/metabolismo
11.
Bull Cancer ; 107(9): 896-903, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32762945

RESUMO

Five to ten percent of lung adenocarcinoma harbor chromosomal rearrangements affecting the ALK, ROS1, NTRK and RET genes. These rearrangements are associated with the production of fusion transcripts that lead to the synthesis of chimeric proteins with constitutive kinase activity. These abnormal proteins induce an oncogenic dependency that may be targeted by tyrosine kinase inhibitors. In this review, we will summarize the clinical and molecular epidemiology of chromosomal rearrangements affecting ALK, ROS1, NTRK and RET genes. We will describe the mechanisms of resistance to tyrosine kinase inhibitors that have been reported. We will present the molecular techniques that can be used to detect these rearrangements and the strategies set-up by the molecular oncology laboratories to diagnose these genetic alterations.


Assuntos
Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Humanos
12.
Protein Cell ; 11(10): 740-770, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32780218

RESUMO

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Assuntos
Envelhecimento/imunologia , Betacoronavirus , Infecções por Coronavirus/imunologia , Sistema Imunitário/imunologia , Pandemias , Pneumonia Viral/imunologia , Análise de Célula Única , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Linfócitos T CD4-Positivos/metabolismo , Linhagem da Célula , Montagem e Desmontagem da Cromatina , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/biossíntese , Citocinas/genética , Suscetibilidade a Doenças , Citometria de Fluxo/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Rearranjo Gênico , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/crescimento & desenvolvimento , Imunocompetência/genética , Inflamação/genética , Inflamação/imunologia , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Análise de Sequência de RNA , Transcriptoma , Adulto Jovem
13.
Nat Commun ; 11(1): 3883, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753598

RESUMO

Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Rearranjo Gênico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Temozolomida/farmacologia , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Animais , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Adutos de DNA/efeitos dos fármacos , Adutos de DNA/metabolismo , Metilação de DNA , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Regiões Promotoras Genéticas/genética , RNA-Seq , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/metabolismo , Regulação para Cima , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
14.
PLoS Genet ; 16(7): e1008949, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32702045

RESUMO

In Paramecium tetraurelia, a large proportion of the germline genome is reproducibly removed from the somatic genome after sexual events via a process involving small (s)RNA-directed heterochromatin formation and DNA excision and repair. How germline limited DNA sequences are specifically recognized in the context of chromatin remains elusive. Here, we use a reverse genetics approach to identify factors involved in programmed genome rearrangements. We have identified a P. tetraurelia homolog of the highly conserved histone chaperone Spt16 subunit of the FACT complex, Spt16-1, and show its expression is developmentally regulated. A functional GFP-Spt16-1 fusion protein localized exclusively in the nuclei where genome rearrangements take place. Gene silencing of Spt16-1 showed it is required for the elimination of all germline-limited sequences, for the survival of sexual progeny, and for the accumulation of internal eliminated sequence (ies)RNAs, an sRNA population produced when elimination occurs. Normal accumulation of 25 nt scanRNAs and deposition of silent histone marks H3K9me3 and H3K27me3 indicated that Spt16-1 does not regulate the scanRNA-directed heterochromatin pathway involved in the early steps of DNA elimination. We further show that Spt16-1 is required for the correct nuclear localization of the PiggyMac (Pgm) endonuclease, which generates the DNA double-strand breaks required for DNA elimination. Thus, Spt16-1 is essential for Pgm function during programmed genome rearrangements. We propose a model in which Spt16-1 mediates interactions between the excision machinery and chromatin, facilitating endonuclease access to DNA cleavage sites during genome rearrangements.


Assuntos
Núcleo Celular/genética , Chaperonas de Histonas/genética , Paramecium/genética , Transposases/genética , Sequência de Bases/genética , Quebras de DNA de Cadeia Dupla , Clivagem do DNA , DNA de Protozoário/genética , Endonucleases , Rearranjo Gênico/genética , Genoma de Protozoário/genética , Paramecium/crescimento & desenvolvimento
16.
Zhonghua Bing Li Xue Za Zhi ; 49(7): 675-680, 2020 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-32610377

RESUMO

Objective: To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors. Methods: Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children's Medical Center, Shanghai Jiaotong University and Singapore KK Women's and Children's Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods. Results: There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months. Conclusions: NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Adolescente , Criança , Pré-Escolar , China , Complexo Dinactina , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Lactente , Masculino , Receptor trkA
18.
Arkh Patol ; 82(3): 18-23, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32593262

RESUMO

AIM OF STUDY: To determine a diagnostic algorithm for detecting translocation of the ALK gene and its frequency in the Moscow region. MATERIALS AND METHODS: During the priod between 2014 and 2018 (inclusive), 488 patients without activating mutations in the EGFR gene in the Moscow region were tested. To detect translocation of the ALK gene, fluorescence in situ hybridization (FISH) methods, an immunohistochemical method, and, in some cases, a polymerase chain reaction were used. RESULTS: Revealed ALK gene rearrangement in a population of patients with lung adenocarcinoma amounted to an average of 7.6% of cases. With this, the main method that we used was immunohistochemical method, applicable in more than 80% of cases. The use of other methods for verification of abnormalities in the ALK gene was found necessary in rare cases (3.3%). CONCLUSIONS: Using the algorithm presented in the article, it was possible to detect ALK gene rearrangement in a population of patients with lung adenocarcinoma in the Moscow region in an average of 7.6% of cases.


Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Moscou , Mutação , Receptores Proteína Tirosina Quinases
19.
Medicine (Baltimore) ; 99(24): e20733, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541525

RESUMO

INTRODUCTION: To investigate the gene rearrangement and mutation of lymphoma biomarkers including (Immunoglobulin H (IgH), Immunoglobulin kappa (IGK), Immunoglobulin lambda (IGL), and TCR) in the lymphoma diagnosis. METHODS AND ANALYSIS: Paraffin tissue samples from 240 cases diagnosed as suspected lymphoma in the department of pathology, Deyang City People's Hospital from June 2020 to June 2021 will be enrolled. Deoxyribonucleic acid extraction and Polymerase Chain Reaction (PCR) amplification will be performed in these paraffin tissue samples. Immunoglobulin and T cell receptor (TCR) rearrangement will be analyzed by hetero-double chain gel electrophoresis and BioMed-2 standardized immunoglobulin gene rearrangement detection system. In this study protocol IGH gene rearrangement, IGK gene rearrangement, both IGH and IGL gene rearrangement, both IGH and IGK gene rearrangement, both IGK and IGL gene rearrangement, both IGH, IGK and IGL gene rearrangement, TCR gene rearrangement and positive Ig/TCR rearrangement will be analyzed. DISCUSSION: In this study, we will use B and T cell lymphoma analysis focusing on IgH, IGK, IGL, and TCR gene rearrangement, so as to provide early guidance for the diagnosis of lymphoma. Second generation sequencing technology is helpful in the differential diagnosis of lymphoma. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2000032366.


Assuntos
Rearranjo Gênico , Linfoma/genética , Mutação , Estudos Observacionais como Assunto/métodos , Projetos de Pesquisa , Humanos , Estudos Prospectivos
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 775-780, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552935

RESUMO

OBJECTIVE: To investigate the clinical characteristics and prognostic influencing factors of adult AML patients with MLL rearrangement. METHODS: Clinical data of 184 adult AML patients with MLL rearrangement treated in our hospital from January 2011 to December 2017 were analyzed retrospectively. The clinical features, immunophenotypic characteristics, cytogenetic characteristics, molecular biological characteristics and gene mutation characteristics were recorded, the survival and prognostic influencing factors of patients were analyzed. RESULTS: Among 184 patients, 94 cases were male, 90 cases were female, median age were 36.0 years, median WBC count were 22.0×109/L, 156 cases as 84.78% for FAB typing M5, and 18 cases as 28.13% for MLL/AF9 gene positive. The median total survival time and recurrence-free survival time of 184 patients were 15.7 months and 13.3 months respectively. The cumulative total survival rate and recurrence-free survival rate by followed-up for 2 years were 36.72% and 29.33% respectively. The cumulative overall survival rate and recurrence-free survival rate of transplant recipients were significantly higher than those of non-transplant recipients by follow-up for 2 years (P<0.05). Univariate analysis showed that age, baseline WBC count, baseline Hb levels, complete remission after one course of treatment and transplantation or no were the influencing factors of overall survival time in adult AML patients with MLL rearrangement (P<0.05). Cox regression model multivariate analysis showed that baseline WBC count, complete remission after one course of treatment, and transplantation or no were the independent influencing factors for overall survival time in adult AML patients with MLL rearrangement(P<0.05). CONCLUSION: Adult AML patients with MLL rearrangement are mostly belong to acute monocytic leukemia, and MLL/AF9 is the most common associated gene. Patients with AML and MLL rearrangement are prone to recurrence after routine chemotherapy. Allo-HSCT treatment is helpful to improve clinical prognosis of patients.


Assuntos
Leucemia Mieloide Aguda , Adulto , Feminino , Rearranjo Gênico , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Proteína de Leucina Linfoide-Mieloide , Prognóstico , Indução de Remissão , Estudos Retrospectivos
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