Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 261
Filter
1.
Journal of Experimental Hematology ; (6): 1450-1455, 2021.
Article in Chinese | WPRIM | ID: wpr-922278

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics, outcomes and prognosis of adult acute myeloid leukemia (AML) patients with NUP98 gene rearrangement.@*METHODS@#The clinical data of adult AML patients with NUP98 gene rearrangement from January 2015 to December 2019 were retrospectively analyzed, including clinical characteristics, laboratory examination, genetic anomaly, treatment strategy and survival.@*RESULTS@#A total of 15 patients with NUP98 gene rearrangement were detected in 410 adult AML patients (3.7%). The ratio of male to female among 15 patients was 1.1∶1, and the median age was 43 (17-76) years old. The main FAB types were M2 and M4/M5, and including one unclassified. According to the genetic prognosis, 11 cases were intermediate risk, while 4 cases were high risk. The main type of NUP98 gene rearrangement was NUP98-HOXA9 (13/15, 86.7%). 10 patients underwent next generation sequencing, in which 5 patients showed epigenetic gene mutations, 3 patients showed FLT3-ITD or WT1 mutations, and 2 patients showed no mutation. After induction therapy, 13 of 15 patients achieved complete remission(CR). 7 of 8 patients with standard induction therapy achieved CR. 7 elder or intolerance patients with demethylation drug and chemotherapy all achieved CR. The median follow-up time was 28 months. The median OS of 15 the patients was 31.5 months (95% CI 10.7%-52.2%), and the median OS of the patients in non-allogeneic hematopoietic stem cell transplantation (Allo-HSCT) group was 18.5 months (95% CI 17.8%-19.1%). The median OS was not reached for the patients in the Allo-HSCT group.@*CONCLUSION@#Allo-HSCT can significantly improve the prognosis of AML patients with NUP98 rearrangement. NUP98 rearrangement can be accompanied by epigenetic gene mutations. For the elderly or patients who do not tolerate standard induction therapy, demethylation drugs combined with chemotherapy can achieve good outcomes.


Subject(s)
Adolescent , Adult , Aged , Female , Gene Rearrangement , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Nuclear Pore Complex Proteins/genetics , Prognosis , Retrospective Studies , Young Adult
2.
Article in Chinese | WPRIM | ID: wpr-880074

ABSTRACT

OBJECTIVE@#To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement.@*METHODS@#A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification.@*RESULTS@#Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×10@*CONCLUSION@#The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.


Subject(s)
Child , Child, Preschool , Disease-Free Survival , Female , Gene Rearrangement , Humans , Male , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Receptors, Cytokine/genetics , Receptors, Purinergic P2Y/genetics
3.
Yonsei Medical Journal ; : 262-266, 2020.
Article in English | WPRIM | ID: wpr-811468

ABSTRACT

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a TPM3-ALK fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for ALK translocation should be performed. This awareness is critically important, because ALK rearrangement confers sensitivity to ALK inhibitors.


Subject(s)
Adolescent , Carcinoma, Renal Cell , Cytoplasm , Eosinophils , Gene Rearrangement , Humans , Kidney , Lymphoma , Nephrectomy , Phosphotransferases , Vacuoles , World Health Organization
4.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-827016

ABSTRACT

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.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
5.
Article in Chinese | WPRIM | ID: wpr-829044

ABSTRACT

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 22.0×10/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.


Subject(s)
Adult , Female , Gene Rearrangement , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Male , Myeloid-Lymphoid Leukemia Protein , Prognosis , Remission Induction , Retrospective Studies
6.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-828746

ABSTRACT

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.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
7.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-828582

ABSTRACT

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.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
8.
Article in Korean | WPRIM | ID: wpr-787518

ABSTRACT

Mucosa-associated lymphoid tissue (MALT) lymphoma has specific clinical and pathologic features. The most common site MALT lymphomas is the stomach; however, it can also occur in other organs, such as the salivary glands. MALT lymphoma is rare, but its prognosis is good. A 32-year-old man visited Konyang university hospital with parotid mass. Superficial partial parotidectomy was performed to exclude lymphoid neoplasms. IgH gene rearrangement analysis of the surgical specimen led to the diagnosis of MALT lymphoma. The patient underwent esophagogastroduodenoscopy, positron emission tomography-computed tomography, and whole-body bone scan. Regional or distant metastasis was not observed on staging workup. The patient underwent postoperative radiation therapy, there has been no recurrence of MALT lymphoma to date. Here, we report this rare case of parotid MALT lymphoma that was treated with surgery and postoperative radiation therapy.


Subject(s)
Adult , Diagnosis , Electrons , Endoscopy, Digestive System , Gene Rearrangement , Humans , Lymphoid Tissue , Lymphoma , Lymphoma, B-Cell, Marginal Zone , Neoplasm Metastasis , Parotid Gland , Prognosis , Recurrence , Salivary Glands , Stomach
9.
Article in Chinese | WPRIM | ID: wpr-776808

ABSTRACT

OBJECTIVE@#To assess the value of detecting the rearrangement of mixed lineage leukemia (MLL) gene in children with acute mononuclear leukemia (AML).@*METHODS@#Dual-color fluorescence in situ hybridization (FISH) probe was used to detect MLL gene rearrangement in 68 children with AML by interphase FISH. The results were compared with that of conventional G banding chromosomal analysis.@*RESULTS@#Among the 68 children, 28 were detected by FISH with positive hybridization signals, with a detection rate for MLL gene rearrangement being 41.2%. Twelve (17.6%) reciprocal translocations and interruption of 11q23 were detected by G banding analysis. The difference in the detection rates between the two methods was statistically significant (P< 0.05).@*CONCLUSION@#The sensitivity of FISH assay for MLL gene rearrangement was significantly higher than that of G banding chromosomal karyotyping. Combined use of both methods for children with AML can improve the detection rate of MLL gene rearrangements and provide crucial clues for clinical diagnosis, treatment and prognosis.


Subject(s)
Child , Chromosomes, Human, Pair 11 , Gene Rearrangement , Histone-Lysine N-Methyltransferase , Genetics , Humans , In Situ Hybridization, Fluorescence , Leukemia, Monocytic, Acute , Genetics , Myeloid-Lymphoid Leukemia Protein , Genetics , Translocation, Genetic
10.
Article in Chinese | WPRIM | ID: wpr-776743

ABSTRACT

OBJECTIVE@#To assess the value of detecting multiple rearrangements of MLL gene in children with acute mononuclear leukemia (AML).@*METHODS@#Eighty six children with AML were analyzed by fluorescence in situ hybridization (FISH), chromosomal karyotyping and multiplex reverse transcription-PCR (RT-PCR).@*RESULTS@#Cross signals were detected by FISH in 26 cases, and 30.2% were detected with MLL gene rearrangements. R-band karyotyping analysis revealed 14 translocations with breakages involving 11q23 and 5 other aberrations, which yielded an overall detection rate of 22.1%. Multiple RT-PCR has detected 12 fusion genes produced by the MLL translocation, which yielded a detection rate of 14.0%. A significant difference was found in the detection rate of the three methods (P< 0.05).@*CONCLUSION@#Combined use of FISH, chromosomal karyotyping and multiplex RT-PCR can improve the detection of MLL gene rearrangements and provide important clues for clinical diagnosis, treatment and prognosis of AML.


Subject(s)
Child , Chromosomes, Human, Pair 11 , Gene Rearrangement , Histone-Lysine N-Methyltransferase , Genetics , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myeloid, Acute , Genetics , Myeloid-Lymphoid Leukemia Protein , Genetics , Translocation, Genetic
11.
Chinese Journal of Lung Cancer ; (12): 329-335, 2019.
Article in Chinese | WPRIM | ID: wpr-775624

ABSTRACT

BACKGROUND@#Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor.@*METHODS@#Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital (PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted.@*RESULTS@#A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough (41/46, 89.1%) and expectoration (35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation (87.0%), patchy consolidation (84.8%), and multiple ground-glass nodules (84.8%). Multiple cystic changes (40%) and cavitation (13%) were also quite frequent. Ipsilateral and contralateral intrapulmonary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days (95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy (TBLB) combined with bronchoalveolar lavage (BAL) had a diagnostic yield of 80.9% (17/21). Sputum cytology had a diagnostic yield of 45% (9/20). Twenty-six cases were invasive mucinous adenocarcinoma (26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8% (6/38) of patients and ALK rearrangement was detected in 3.0% (1/33) of patients. The median overall survival for these patients was 522 d (95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival (HR=0.155, P=0.002,2). The median overall survival was 547 d (95%CI: 492-602 d) with chemotherapy and 331 d (95%CI: 22-919) without chemotherapy.@*CONCLUSIONS@#Diagnosis of pneumonic-type carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival.


Subject(s)
Aged , Anaplastic Lymphoma Kinase , Genetics , Metabolism , Antineoplastic Agents , Therapeutic Uses , Carcinoma , Diagnostic Imaging , Drug Therapy , Genetics , Pathology , ErbB Receptors , Genetics , Metabolism , Female , Gene Rearrangement , Humans , Lung Neoplasms , Diagnostic Imaging , Drug Therapy , Genetics , Pathology , Male , Middle Aged , Mutation , Neoplasm Staging , Retrospective Studies , Survival Analysis , Tomography, X-Ray Computed
12.
Article in English | WPRIM | ID: wpr-719287

ABSTRACT

Lung cancer remains a leading cause of cancer mortality worldwide, including in Korea. Systemic therapy including platinum-based chemotherapy and targeted therapy should be provided to patients with stage IV non-small cell lung cancer (NSCLC). Applications of targeted therapy, such as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and anaplastic lymphoma kinase (ALK) inhibitors, in patients with NSCLC and an EGFR mutation or ALK gene rearrangement has enabled dramatic improvements in efficacy and tolerability. Despite advances in research and a better understanding of the molecular pathways of NSCLC, few effective therapeutic options are available for most patients with NSCLC without druggable targets, especially for patients with squamous cell NSCLC. Immune checkpoint inhibitors such as anti-cytotoxic T lymphocyte antigen-4 or anti-programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have demonstrated durable response rates across a broad range of solid tumors, including NSCLC, which has revolutionized the treatment of solid tumors. Here, we review the current status and future approaches of immune checkpoint inhibitors that are being investigated for NSCLC with a focus on pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Therapy , Epithelial Cells , Gene Rearrangement , Humans , Immunotherapy , Korea , Lung Neoplasms , Lymphocytes , Lymphoma , Mortality , Phosphotransferases , Protein-Tyrosine Kinases , ErbB Receptors
13.
Arch. endocrinol. metab. (Online) ; 62(6): 623-635, Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-983814

ABSTRACT

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Germ-Line Mutation/genetics , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/genetics , Proto-Oncogene Proteins c-ret/genetics , Genetic Carrier Screening/methods , Time Factors , Brazil , Thyroid Neoplasms/pathology , Immunohistochemistry , Transfection/methods , Gene Rearrangement/genetics , Reproducibility of Results , Risk Factors , Age Factors , Carcinoma, Neuroendocrine/pathology , Risk Assessment , Early Detection of Cancer , Genetic Association Studies
14.
Prensa méd. argent ; 104(10): 478-488, dic 2018. fig
Article in Spanish | LILACS, BINACIS | ID: biblio-1046959

ABSTRACT

Las inversiones son reordenamientos intracromosómicos originados por dos rupturas en un cromosoma seguidas de la reinserción del fragmento rotado en 180º. Dependiendo si involucra o no al centrómero pueden ser pericén tricas o paracéntricas. La incidencia es 0.09 a 0.49/1.000. Las inversiones son rearreglos estructurales aparentemente equilibrados, por lo que la mayoría de los individuos portadores tienen fenotipos normales y una minoría tienen fenotipos patológicos (probablemente por alteración en la secuencia de genes o variación en la función de éstos por efectos de cambio de posición). Se presentan tres casos de inversiones detectas por la técnica de Bandeo G y confirmadas por Hibridación In Situ Fluorescente (FISH). Caso 1: INVERSION PARACENTRICA FAMILIAR DEL CROMOSOMA 13 ASOCIADA A RETRASO MENTAL Y DISMORFIAS. El exhaustivo análisis del árbol genealógico y el estudio cromosómico al mayor número posible de individuos permitió confirmar la asociación inversión/fenotipo patológico en este grupo familiar. 13 de 17 miembros son portadores de inv(13)(q31q32)inh.ish inv(13)(q31q32) (wcp13+). Caso 2: INVERSION PARACENTRICA DEL CROMOSOMA 6 DE NOVO EN RECIEN NACIDO CON RETRASO MADURATIVO GLOBAL Y RETRASO DEL CRECIMIENTO INTRAUTERINO. En este caso no es posible adjudicar que, el fenotipo afectado se deba a la inversión. Cariotipo: 46,XY,add(6)(q21)dn.ish inv(6)(q21q27)(wcp6+). Caso 3: INVERSION PERICENTRICA DEL CROMOSOMA 12 EN OVODONANTE. Dicha inversión no parece tener efecto sobre el fenotipo, ya que es una paciente con coeficiente intelectual normal y no presenta malformaciones congénitas. Cariotipo: 46,XX,inv(12)(p12q14).ish inv(12) (p12q14)(wcp12+). Este reporte de casos muestra los tres fenotipos posibles de una inversión: patológico, dudoso y normal. Es el primer reporte de una inv(13) que confiera fenotipo patológico.


The inversions are intrachromosomal rearrangements which occur when a single chromosome undergoes two breaks and the region between it's rotates 180 degrees before rejoining. Depending on whether or not it include the centromere, they can be pericentric or paracentric. The incidence is 0.09 to 0.49/1,000. The inversions are apparently balanced structural rearrangements, so the most of the carrier individuals show normal phenotypes and a minority have pathological phenotypes (probably due to variation in their function due to changes in position). Three cases of inversions detected by the G Banding technique and confirmed by Fluorescence In Situ Hybridization (FISH) are presented. Case 1: FAMILIAL PARACENTRIC INVERSION OF CHROMOSOME 13 ASSOCIATED WITH MENTAL RETARDATION AND DISMORPHIA. The exhaustive analysis of the pedigree and the chromosomal study to the greatest possible number of individuals confirmed the inversion/pathological phenotype association in this family group. 13 of 17 members are carriers of inv(13)(q31q32)inh.ish inv(13)(q31q32)(wcp13+). Case 2: PARACENTRAL INVERSION DE NOVO OF CHROMOSOME 6 IN NEWBORN WITH GLOBAL MATURITY DELAY AND DELAY OF INTRAUTERINE GROWTH. In this case it is not possible to adjudge that, the affected phenotype is due to the inversion. Karyotype: 46,XY,add(6)(q21)dn.ish inv(6)(q21q27)(wcp6+). Case 3: PERICENTRIC INVERSION OF CHROMOSOME 12 IN OVODONANT. This inversion does not seem to have an effect on the phenotype, since it is a patient with normal IQ and does not present congenital malformations. Karyotype: 46,XX,inv(12)(p12q14).ish inv(12) (p12q14)(wcp12+). This case report shows the three possible phenotypes of an inversion: pathological, questionable and normal. It is the first report of an inv(13) that confers pathological phenotype. Key words: chromosomal inversion, G Banding, phenotype, structural rearrangement, fluorescence in situ hybridization.


Subject(s)
Phenotype , Gene Rearrangement/genetics , Chromosome Banding , In Situ Hybridization, Fluorescence , Chromosomes, Human, Pair 6 , Chromosomes, Human, Pair 12 , Chromosomes, Human, Pair 13
15.
Rev. cienc. forenses Honduras (En línea) ; 4(1): 11-17, 2018. graf., ilus
Article in Spanish | LILACS, BIMENA | ID: biblio-1290609

ABSTRACT

La influenza continúa siendo una causa importante de muerte en las Américas; en nuestro país al igual que en otros países del continente, hay circulación viral sostenida del virus Influenza A H1N1pdm09, este reporte describe los hallazgos histopatológicos más relevantes, encontrados en femenina de 32 años de edad, con antecedentes de anemia drepanocítica; que falleció tres días después de inicio de síntomas respiratorios. La autopsia estableció como causa de muerte neumonía, daño alveolar difuso (DAD), edema, hemorragia, membranas hialinas y colonias bacterianas secundarias a infección por virus Influenza AH1N1pdm09. Este reporte destaca la importancia que el médico forense realice una labor integrativa, de los hallazgos macro y microscópicos y exámenes complementarios de la autopsia en el contexto epidemiológico y clínico en el que se dan los decesos...(AU)


Subject(s)
Humans , Female , Adult , Autopsy/methods , Influenza A Virus, H1N1 Subtype , Gene Rearrangement/genetics , Morphological and Microscopic Findings
16.
Article in Korean | WPRIM | ID: wpr-718773

ABSTRACT

Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.


Subject(s)
Achondroplasia , Acidosis, Lactic , Angelman Syndrome , Apolipoproteins , Brain Diseases , Breast , Deafness , Education , Epilepsies, Myoclonic , Fragile X Syndrome , Gene Rearrangement , Hearing Loss , Hepatolenticular Degeneration , Huntington Disease , Janus Kinase 2 , Korea , Laboratory Proficiency Testing , Leukemia , Li-Fraumeni Syndrome , Methylenetetrahydrofolate Reductase (NADPH2) , Molecular Biology , Multiple Endocrine Neoplasia , Muscular Atrophy, Spinal , Muscular Disorders, Atrophic , Muscular Dystrophy, Duchenne , Optic Atrophy, Hereditary, Leber , Ovarian Neoplasms , Pathology, Molecular , Phosphotransferases , Quality Control , Quality Improvement , Spinocerebellar Ataxias , Vascular Endothelial Growth Factor Receptor-1
17.
Braz. j. med. biol. res ; 50(1): e5426, 2017. tab, graf
Article in English | LILACS | ID: biblio-839242

ABSTRACT

IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL). Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD) after induction chemotherapy. Seventeen consecutive newly diagnosed B-ALL patients were investigated by multiplex PCR assay and real time quantitative PCR according to BIOMED 2 conditions. The vast majority of clonal VH-JH rearrangements included VH3 gene. For IGK deletion, clonal VK1f/6-Kde recombinations were mainly identified. These rearrangements were quantified to follow-up seven B-ALL after induction using patient-specific ASO. Four patients had an undetectable level of MRD with a sensitivity of up to 10-5. This molecular approach allowed identification of prognosis risk group and adequate therapeutic decision. The IGK-Kde and IGH gene rearrangements might be used for diagnosis and MRD monitoring of B-ALL, introduced for the first time in Tunisian laboratories.


Subject(s)
Humans , Male , Female , Child, Preschool , Adolescent , Middle Aged , Biomarkers, Tumor/genetics , Gene Rearrangement/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity
18.
Article in Korean | WPRIM | ID: wpr-155824

ABSTRACT

Myeloid neoplasia with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) rearrangements is an uncommon Philadelphia-negative myeloproliferative neoplasm. Their most common morphological diagnosis is chronic myelomonocytic leukemia with eosinophilia, which is associated with t(5;12)(q33;p13) and results in the formation of the ETV6-PDGFRB fusion gene. Here, we report a 49-year-old man with a myeloid neoplasm with a PDGFRB rearrangement, who was incidentally diagnosed with hyperleukocytosis and eosinophilia during a health screening. A chromosome analysis of a bone marrow sample revealed 46, XY, t(5;12)(q33;p13), and fluorescence in situ hybridization analysis revealed the PDGFRB gene rearrangement. The patient was treated with imatinib and subsequently achieved complete hematological and molecular remission.


Subject(s)
Bone Marrow , Diagnosis , Eosinophilia , Fluorescence , Gene Rearrangement , Humans , Imatinib Mesylate , In Situ Hybridization , Leukemia, Myelomonocytic, Chronic , Mass Screening , Middle Aged , Myeloproliferative Disorders , Receptor, Platelet-Derived Growth Factor beta , Receptors, Platelet-Derived Growth Factor
19.
Blood Research ; : 55-61, 2017.
Article in English | WPRIM | ID: wpr-226881

ABSTRACT

BACKGROUND: This study characterized clonal IG heavy V-D-J (IGH) gene rearrangements in South Indian patients with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) and identified age-related predominance in VDJ rearrangements. METHODS: IGH rearrangements were studied in 50 precursor B-ALL cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction (PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement sequences were analyzed using the IMGT/V-QUEST tool. RESULTS: Clonal IGH rearrangements were detected in 41 (82%) precursor B-ALL cases. Among the IGHV1-IGHV7 subgroups, IGHV3 was used in 25 (50%) cases. Among the IGHD1-IGHD7 genes, IGHD2 and IGHD3 were used in 8 (40%) and 5 (25%) clones, respectively. Among the IGHJ1-IGHJ6 genes, IGHJ6 and IGHJ4 were used in 9 (45%) and 6 (30%) clones, respectively. In 6 out of 20 (30%) IGH rearranged sequences, CDR3 was in frame whereas 14 (70%) had rearranged sequences and CDR3 was out of frame. A somatic mutation in Vmut/Dmut/Jmut was detected in 14 of 20 IGH sequences. On average, Vmut/Dmut/Jmut were detected in 0.1 nt, 1.1 nt, and 0.2 nt, respectively. CONCLUSION: The IGHV3 gene was frequently used whereas lower frequencies of IGHV5 and IGHV6 and a higher frequency of IGHV4 were detected in children compared with young adults. The IGHD2 and IGHD3 genes were over-represented, and the IGHJ6 gene was predominantly used in precursor-B-ALL. However, the IGH gene rearrangements in precursor-B-ALL did not show any significant age-associated genotype pattern attributed to our population.


Subject(s)
Child , Clone Cells , Complementarity Determining Regions , Gene Rearrangement , Genotype , Heteroduplex Analysis , Humans , Immunoglobulins , Polymerase Chain Reaction , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cells, B-Lymphoid , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL