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1.
Medicine (Baltimore) ; 100(6): e24560, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578551

RESUMO

ABSTRACT: In the literature, 7q11 deletion was reported with various abnormalities. However, there were other genetic conditions combined with 7q11.21. It is necessary to have sufficient pure 7q11.21 microdeletions for classifying the pathogenic categories of variation.Chromosomal karyotyping analysis was performed on cultured amniotic fluid cells. Eighteen pregnant women took chromosomal microarray using prenatal amniotic fluid samples at our center by Affymetrix CytoScan750K_Array. We followed the outcome of these pregnancies and determined postnatal health conditions.Cytogenetic studies delineated that all patients had normal karyotypes. The exception was P17, who had 47, XN. Single nucleotide polymorphism array results showed 517 to 605 kb deletions of 7q11.21 (chr7: 64543313-65196780) in these cases. The microarray results were pure or combined 7q11.21 microdeletions. In 11 pure 7q11.21 microdeletions and 7 combined cases, there was no apparent abnormal phenotype associated with partial 7q11.21. Among them, only mothers of P10 and P17 decided to terminate the pregnancies due to 18 trisomy or ultrasound abnormal fetal strephenopodia. In the follow-up survey, the newborns had no apparent abnormalities.In this study, we described 11 pure and 7 combined 7q11.21 microdeletions associating with no apparent postnatal phenotypic abnormalities. From this study, we can learn that the partial 7q11.21 deletion (chr7: 64543313-65196780) might be benign and have no association with human disorders.


Assuntos
Cromossomos Humanos Par 7 , Diagnóstico Pré-Natal , Sequência de Bases , Feminino , Humanos , Cariotipagem , Análise em Microsséries , Gravidez , Deleção de Sequência
2.
Cancer Sci ; 112(4): 1383-1389, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33583097

RESUMO

Revertant (somatic) mosaicism is a spontaneous correction of a causative mutation in patients with congenital diseases. A relatively frequent event, revertant mosaicism may bring favorable outcomes that ameliorate disorders, and is therefore called "natural gene therapy." However, it has been revealed recently that "overcorrection" of inherited bone marrow failure in patients with sterile alpha motif domain containing 9 (SAMD9)/9L syndromes by revertant mosaicism induces myelodysplastic syndrome (MDS) with monosomy 7 that occasionally proceeds to acute myelogenous leukemia (AML). In this review, we interpret very complex mechanisms underlying MDS/AML in patients with SAMD9/9L syndromes. This includes multiple myeloid tumor suppressors on the long arm of chromosome 7, all of which act in a haploinsufficient fashion, and a difference in sensitivity to interferon between cells carrying a mutation and revertants. Overcorrection of mutants by somatic mosaicism is likely a novel mechanism in carcinogenesis.


Assuntos
Carcinogênese/genética , Leucemia Mieloide Aguda/genética , Mutação/genética , Animais , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mosaicismo , Síndromes Mielodisplásicas/genética , Proteínas Supressoras de Tumor/genética
3.
Medicine (Baltimore) ; 100(7): e24382, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607772

RESUMO

INTRODUCTION: Subchromosomal deletions and duplications could currently be detected by noninvasive preliminary screening (NIPS). However, NIPS is a screening test that requires further diagnosis. Here we report a fetus with an autosomal abnormality revealed by NIPS and conventional karyotype combined with copy number variations sequencing (CNV-seq) confirmed the fetus with an unbalanced translocation. PATIENT CONCERN: This was the fourth pregnancy of a 30-year-old woman who underwent 2 spontaneous abortions and gave birth to a child with a normal phenotype. The woman and her husband were healthy and nonconsanguineous. NIPS indicated a repeat of about 19-Mb fragment at the region of 16q22.1-q22.4 at 17-week gestation. DIAGNOSES: The combination of traditional karyotype and CNV-seq could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XX,der(7)t(7;16)(p22;q23) and CNV-seq results showed an approximately 20.96-Mb duplication in 16q22.1-q24.3 (69200001-90160000) and an approximately 3.86-Mb deletion in 7p22.3-p22.2 (40001-3900000). Prenatal ultrasound revealed the fetal micrognathia. The paternal karyotype was 46,XY, t (7;16) (p22;q23), while the maternal was normal. The fetus inherited an abnormal chromosome 7 from its father. INTERVENTIONS: No treatment for the fetus. OUTCOMES: Pregnancy was terminated. CONCLUSIONS: To our knowledge, the occurrence of de novo partial trisomy 16q (16q22.1-qter) and partial monosomy 7p (7p22.2-pter) has not previously been reported up to now. Here, we present the perinatal findings of such a case and a review of the literatures. CNV-seq combined with karyotype is a useful tool for chromosomal abnormalities indicated by NIPS.


Assuntos
Cromossomos Humanos Par 7/genética , Monossomia/diagnóstico , Trissomia/genética , Aborto Eugênico , Adulto , Amniocentese , Cromossomos Humanos Par 16/genética , Feminino , Humanos , Gravidez , Translocação Genética/genética , Trissomia/diagnóstico , Sequenciamento Completo do Genoma
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 855-858, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761594

RESUMO

OBJECTIVE: To explore the genetic basis for a child with multiple malformation and growth retardation. METHODS: The child was subjected to low-coverage massively parallel copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS) technique. RESULTS: G-banding karyotyping analysis has found no abnormality in the boy and his parents. CNV-seq analysis discovered that the child has carried a heterozygous 4.36 Mb deletion (24 020 000-28 380 000) at 7p15.3p15.1. The same deletion was not found in either parent. The deletion has encompassed 28 OMIM genes including HOXA13, CYCS, DFNA5, HOXA11 and HOXA2. Among these, HOXA13 has been associated with distal limb deformity, hypospadias and cryptorchidism. HOXA1, HOXA3 and HOXA4 are involved in the formation of cardiac primordia and primordial tube, and HOXA2 is involved in the development of auditory system. The clinical phenotype of the child was consistent with that of 7p15 deletion syndrome. CONCLUSION: Haploinsufficiency of HOXA1, HOXA2, HOXA3, HOXA4 and HOXA13 genes may underlie the clinical phenotype of the child, which is comparable to 7p15 deletion syndrome.


Assuntos
Anormalidades Múltiplas , Deleção Cromossômica , Variações do Número de Cópias de DNA , Anormalidades Múltiplas/genética , Criança , Bandeamento Cromossômico , Cromossomos Humanos Par 7 , Haploinsuficiência , Proteínas de Homeodomínio/genética , Humanos , Cariotipagem , Masculino , Fenótipo
6.
Leuk Res ; 95: 106387, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535247

RESUMO

A relatively small subset of myeloid neoplasms involve rearrangements of cytoband 3q26.2. Such rearrangements are often in response to therapy and carry a poor prognosis. The ectopic expression of MECOM is the result of such translocations. To date, thirty-three t(3;8)(q26.2;q24) cases have been reported; we contribute two patients with confirmed MECOM and MYC rearrangements. Both patients presented with pancytopenia and were diagnosed with myelodysplastic/myeloproliferative disorders. In addition to translocation t(3;8), Patient 1 possessed a derivative chromosome 5, while Patient 2 possessed monosomy 7; neither patient's clonal abnormalities resolved in follow-up studies. Of the previous 33 cases, one exhibited 5q loss, while monosomy 7 was found in fifteen. These findings contribute to the small number of reported cases with t(3;8) translocations. We also speculate about the molecular mechanisms associated with this translocation.


Assuntos
Proteína do Locus do Complexo MDS1 e EVI1/genética , Doenças Mieloproliferativas-Mielodisplásicas/genética , Idoso , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 7/genética , Genes myc/genética , Humanos , Masculino , Pessoa de Meia-Idade , Translocação Genética
7.
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
8.
Hematology ; 25(1): 165-167, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32338586

RESUMO

We present the case of a patient with aplastic anemia (AA) who was treated with eltrombopag. To the best of our knowledge, this is the first report of the disappearance of monosomy 7 after eltrombopag treatment. The patient was a 77-year-old woman with intraoral hematoma and purpura who was diagnosed with very severe AA with a normal karyotype. After combination therapy with rabbit antithymocyte globulin, cyclosporin, and granulocyte-colony-stimulating factor (G-CSF), pancytopenia transiently improved. When pancytopenia worsened again, the patient was administered darbepoetin alfa for renal anemia and danazol. Bone marrow examination showed 2.5% blasts with the karyotype 45,XX,-7[17]/46,XX[3], and 87.0% of marrow cells had monosomy 7, as determined by 7q31 interphase fluorescence in situ hybridization (FISH) analysis. Pancytopenia was considered owing to the evolution of myelodysplastic syndrome, and we stopped G-CSF and darbepoetin treatment. As she refused treatment with a hypomethylating agent, considering her age, eltrombopag was started against refractory pancytopenia after obtaining informed consent. She showed an improvement in pancytopenia and became transfusion independent. After 1 year of eltrombopag treatment, bone marrow examination revealed 0.7% blasts with the karyotype 46,XX[20] and without monosomy 7 clone by FISH analysis. After a further 1 year of eltrombopag treatment with dose tapering, she has achieved a complete response. This case suggested that eltrombopag treatment is not necessarily contraindicated in patients with monosomy 7.


Assuntos
Anemia Aplástica/complicações , Benzoatos/efeitos adversos , Hidrazinas/efeitos adversos , Pirazóis/efeitos adversos , Idoso , Deleção Cromossômica , Cromossomos Humanos Par 7/efeitos dos fármacos , Feminino , Humanos
9.
Cancer Commun (Lond) ; 40(4): 167-180, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32279463

RESUMO

BACKGROUND: The preoperative prediction of muscular invasion status is important for adequately treating bladder cancer (BC) but nevertheless, there are some existing dilemmas in the current preoperative diagnostic accuracy of BC with muscular invasion. Here, we investigated the potential association between the fluorescence in situ hybridization (FISH) assay and muscular invasion among patients with BC. A cytogenetic-clinical nomogram for the individualized preoperative differentiation of muscle-invasive BC (MIBC) from non-muscle-invasive BC (NMIBC) is also proposed. METHODS: All eligible BC patients were preoperatively tested using a FISH assay, which included 4 sites (chromosome-specific centromeric probe [CSP] 3, 7, and 17, and gene locus-specific probe [GLP]-p16 locus). The correlation between the FISH assay and BC muscular invasion was evaluated using the Chi-square tests. In the training set, univariate and multivariate logistic regression analyses were used to develop a cytogenetic-clinical nomogram for preoperative muscular invasion prediction. Then, we assessed the performance of the nomogram in the training set with respect to its discriminatory accuracy and calibration for predicting muscular invasion, and clinical usefulness, which were then validated in the validation set. Moreover, model comparison was set to evaluate the discrimination and clinical usefulness between the nomogram and the individual variables incorporated in the nomogram. RESULTS: Muscular invasion was more prevalent in BC patients with positive CSP3, CSP7 and CSP17 status (OR [95% CI], 2.724 [1.555 to 4.774], P < 0.001; 3.406 [1.912 to 6.068], P < 0.001 and 2.483 [1.436 to 4.292], P = 0.001, respectively). Radiology-determined tumor size, radiology-determined clinical tumor stage and CSP7 status were identified as independent risk factors of BC muscular invasion by the multivariate regression analysis in the training set. Then, a cytogenetic-clinical nomogram incorporating these three independent risk factors was constructed and was observed to have satisfactory discrimination in the training (AUC 0.784; 95% CI: 0.715 to 0.853) and validation (AUC 0.743; 95% CI: 0.635 to 0.850) set. The decision curve analysis (DCA) indicated the clinical usefulness of our nomogram. In models comparison, using the receiver operator characteristic (ROC) analyses, the nomogram showed higher discriminatory accuracy than any variables incorporated in the nomogram alone and the DCAs also identified the nomogram as possessing the highest net benefits at wide range of threshold probabilities. CONCLUSION: CSP7 status was identified as an independent factor for predicting muscular invasion in BC patients and was successfully incorporated in a clinical nomogram combining the results of the FISH assay with clinical risk factors.


Assuntos
Cromossomos Humanos Par 7/metabolismo , Hibridização in Situ Fluorescente/métodos , Neoplasias da Bexiga Urinária/genética , Idoso , Aneuploidia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia
10.
PLoS One ; 15(4): e0231419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32282835

RESUMO

Barrett's esophagus is the only known mucosal precursor for the highly malignant esophageal adenocarcinoma. Malignant degeneration of non-dysplastic Barrett's esophagus occurs in < 0.6% per year in Dutch surveillance cohorts. Therefore, it has been proposed to increase the surveillance intervals from 3 to 5 years, potentially increasing development of advanced stage interval cancers. To prevent such cases robust biomarkers for more optimal stratification over longer follow up periods for non-dysplastic Barrett's patients are required. In this multi-center study, aberrations for chromosomes 7, 17, and structural abnormalities for c-MYC, CDKN2A, TP53, Her-2/neu and 20q assessed by DNA fluorescence in situ hybridization on brush cytology specimens, were used to determine marker scores and to perform clonal diversity measurements, as described previously. In this study, these genetic biomarkers were combined with clinical variables and analyzed to obtain the most efficient cancer prediction model after an extended period of follow-up (median time of 7 years) by applying Cox regression modeling, bootstrapping and leave-one-out analyses. A total of 334 patients with Barrett's esophagus without dysplasia from 6 community hospitals (n = 220) and one academic center (n = 114) were included. The annual progression rate to high grade dysplasia and/or esophageal adenocarcinoma was 1.3%, and to adenocarcinoma alone 0.85%. A prediction model including age, Barrett circumferential length, and a clonicity score over the genomic set including chromosomes 7, 17, 20q and c-MYC, resulted in an area under the curve of 0.88. The sensitivity and specificity of this model were 0.91 and 0.38. The positive and negative predictive values were 0.13 (95% CI 0.09 to 0.19) and 0.97 (95% CI 0.93 to 0.99). We propose the implementation of the model to identify non-dysplastic Barrett's patients, who are required to remain in surveillance programs with 3-yearly surveillance intervals from those that can benefit from less frequent or no surveillance.


Assuntos
Esôfago de Barrett/diagnóstico , Biomarcadores/metabolismo , Adulto , Idoso , Área Sob a Curva , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 7/genética , Progressão da Doença , Neoplasias Esofágicas/diagnóstico , Feminino , Seguimentos , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Países Baixos , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-myc/genética , Curva ROC , Fatores de Risco
11.
Anticancer Res ; 40(3): 1239-1245, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132020

RESUMO

BACKGROUND/AIM: Since the first description of five pericytomas with the t(7;12)/ACTB-GLI1 fusion gene, only three new tumors were studied by both cytogenetics and molecular techniques. We report here genetic data on another case of this rare tumor. MATERIALS AND METHODS: Cytogenetic, fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing analyses were performed. RESULTS: The pericytoma carried two structurally rearranged chromosomes: der(7)t(7;12)(p22;q13) and der(12)t(1;12)(q12;q13). In FISH experiments with a break-apart probe for GLI1, the distal part of the probe hybridized to der(7) whereas the proximal part to der(12). RT-PCR and Sanger sequencing detected an ACTB-GLI1 fragment in which exon 2 of ACTB was fused to exon 6 of GLI1. CONCLUSION: The ACTB-GLI1 fusion gene was mapped at der(7)t(7;12)(p22;q13) and coded for a putative ACTB-GLI1 protein in which the first 41 amino acid (aa) of ACTB replaced the first 177 aa of GLI1.


Assuntos
Actinas/genética , Proteínas de Fusão Oncogênica/genética , Pericitos/patologia , Neoplasias de Tecidos Moles/genética , Proteína GLI1 em Dedos de Zinco/genética , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 7 , Feminino , Humanos , Neoplasias de Tecidos Moles/patologia , Coxa da Perna/patologia , Translocação Genética
12.
J Pediatr Hematol Oncol ; 42(3): 170-174, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32134844

RESUMO

The distinction between myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) often relies on an arbitrary marrow blast cutoff of 30% in pediatrics and 20% in adults. There is little data about the treatment of children with extramedullary myeloid malignancy that has features of both, MDS and AML. Herein, we report for the first time 2 patients MDS/AML (1 with Shwachman-Diamond syndrome and 1 with idiopathic MDS and monosomy 7) who presented with extramedullary complications, received treatment with azacitidine, achieved complete remission and subsequently underwent hematopoietic stem cell transplantation.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Adolescente , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 7 , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Síndromes Mielodisplásicas/genética , Síndrome de Shwachman-Diamond/complicações
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 462-466, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219838

RESUMO

OBJECTIVE: To analyze the clinical feature of a fetus with split hand-foot malformation (SHFM) and to explore its etiology. METHODS: Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed. Genomic copy number variations (CNVs) of the fetus was analyzed by next-generation sequencing (NGS). Its parents were subjected to chromosomal karyotyping, NGS and fluorescence in situ hybridization (FISH) assays. Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs. RESULTS: Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a V-shape, which was suggestive of SFHM. The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region. FISH and NGS analysis of both parents were normal. Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene, while the copy numbers of SEM1, DLX5 and DLX6 genes were normal. CONCLUSION: The 7q21.3 microdeletion probably underlies the SHFM of the fetus, which has a de novo origin.


Assuntos
Cromossomos Humanos Par 7/genética , Dineínas do Citoplasma/genética , Deformidades Congênitas dos Membros/genética , Deleção Cromossômica , Variações do Número de Cópias de DNA , Feto , Humanos , Hibridização in Situ Fluorescente , Cariotipagem
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 475-478, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219841

RESUMO

OBJECTIVE: To explore the genetic basis for a child with supravalvular aortic stenosis. METHODS: The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings. CONCLUSION: The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.


Assuntos
Estenose Aórtica Supravalvular/genética , Deleção de Genes , Síndrome de Williams/genética , Criança , Bandeamento Cromossômico , Cromossomos Humanos Par 7/genética , Hibridização Genômica Comparativa , Testes Genéticos , Humanos , Síndrome de Williams/complicações
15.
Asian Pac J Cancer Prev ; 21(3): 639-645, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212788

RESUMO

OBJECTIVE: Chromosome detection is important in the diagnosis and prognosis of Myelodysplastic syndrome (MDS) patients. About 50% of MDS patients have chromosomal abnormalities. Moreover, chromosome 5 and 7 are common genetic abnormalities in MDS patients and use to identify prognosis risk group and the proper treatment in MDS patients. The objective of this study was to evaluate chromosomal abnormalities and clinical features of MDS patients in upper northern Thailand. METHODS: Fifty bone marrow (BM) specimens were examined by conventional cytogenetic (CC) technique and fluorescence in situ hybridization (FISH) technique for detected chromosome 5 and 7 abnormalities. The clinical features were comparison between MDS patients with chromosomal abnormalities and those with normal karyotype. RESULTS: Chromosomal abnormalities were detected in 8/50 MDS patients by CC and 17/50 cases by FISH technique. When the CC and FISH techniques were combined, chromosomal abnormalities increased to 21/50 cases.  Abnormalities of isolated chromosome 5 were found in 13 cases and were associated with lower level of percentage blast of BM (p = 0.003) and higher level of hemoglobin (p = 0.019). Moreover, abnormalities of chromosome 7 were found in 3 cases, 1 case of isolated del(7q) and 2 cases of -7 and del(7q) with complex abnormalities. These three cases were associated with higher level of percentage blast of BM (p = 0.010). CONCLUSION: This study showed the frequency and pattern of chromosomal abnormalities of MDS patients in upper northern Thailand were different from other populations. MDS with isolated chromosome 5 abnormalities had clinical characteristics corresponding with patients in good prognosis risk group. However, MDS patients with chromosome 7 and complex abnormalities showed higher percentage blast of BM which high risk to progression to acute myeloid leukemia (AML). Combined CC and FISH techniques detect chromosomal abnormalities with greater frequency than when either technique is used alone.
.


Assuntos
Aberrações Cromossômicas , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Tailândia
16.
Rev. Univ. Ind. Santander, Salud ; 52(1): 51-59, ene.-mar. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1092273

RESUMO

Resumen Introducción: La incidencia de las anomalías congénitas es de 0,5% dentro de los cuales el 0,1-0,3% corresponden a anomalías cromosómicas estructurales, entre ellas están las translocaciones no balanceadas en las que hay pérdida o ganancia de información genética que da como resultado manifestaciones fenotípicas con compromiso en la salud de quienes las padecen. Reporte de caso: Se describe un paciente escolar con una translocación no balanceada t(5;7) (q22;p15) de origen paterno y sus repercusiones. Discusión: Cuando existen reordenamientos en el material genético, las manifestaciones clínicas están ligadas a la localización de los puntos de ruptura y como consecuencia a los genes que estén incluidos en estos segmentos, tal como se presentó en nuestro caso índice. Conclusiones: Es importante el estudio de estos pacientes ya que deben permanecer en vigilancia médica por el riesgo de desarrollar patologías relacionadas con alteraciones en los genes implicados en el reordenamiento genético.


Abstract Introduction: The incidence of congenital anomalies is 0,5%, wich 0,1 to 0,3% belong to structural chromosomic anomalies, between these are unbalanced translocations in which there are loss or gain of genetic information that results in phenotypic manifestations with health compromise of whom suffer it. Case report: A scholar patient with an unbalanced translocation t(5;7) (q22;p15) of paternal origin and its repercussions is described. Discussion: When there are rearrangements in genetic material, the clinical manifestations are linked to breakpoints localizations and as consequence to the genes included in this segments, as presented in our index case. Conclusions: The study of these patients is important because they must remain under medical surveillance due the risk of developing pathologies related with gene alterations implicated in the genetic rearrangement.


Assuntos
Humanos , Translocação Genética , Anormalidades Congênitas , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Cariótipo
17.
Taiwan J Obstet Gynecol ; 59(1): 146-149, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039784

RESUMO

OBJECTIVE: We present mosaic double trisomy involving trisomy 7 and trisomy 20 at amniocentesis in a pregnancy with a favorable outcome. CASE REPORT: A 41-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 48,XY,+7,+20[6]/46,XY[26] in cultured amniocytes. At 19 weeks of gestation, repeat amniocentesis was performed, which revealed a result of 48,XY,+7,+20[4]/46,XY[21] in cultured amniocytes. Simultaneous molecular cytogenetic analyses on uncultured amniocytes at repeat amniocentesis revealed no genomic imbalance in array comparative genomic hybridization (aCGH) analysis, no trisomy 7 and no trisomy 20 signals in 114/114 cells in interphase fluorescence in situ hybridization (FISH) analysis, and no uniparental disomy (UPD) 7 and no UPD 20 in quantitative fluorescent polymerase chain reaction (QF-PCR) analysis. Interphase FISH analysis on cultured amniocytes revealed double trisomy of trisomy 7 and trisomy 20 in 5/105 cells (4.7%) compared with 0/100 cells (0%) in the normal control. Prenatal ultrasound findings were unremarkable. The parental karyotypes were normal. The woman decided to continue the pregnancy, and a healthy 2880-g phenotypically normal male baby was delivered at 34 weeks of gestation without any structural abnormality. The cord blood had a normal karyotype. Interphase FISH analysis of the urinary cells revealed no trisomy 7 and no trisomy 20 signals in 51/51 urinary cells. CONCLUSION: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes can occur in mosaicism for double trisomy involving trisomy 7 and trisomy 20 at amniocentesis. Molecular cytogenetic analyses such as aCGH, FISH and QF-PCR on uncultured amniocytes are useful for rapid distinguishing true mosaicism from pseudomosaicism under such a circumstance.


Assuntos
Amniocentese/métodos , Âmnio/citologia , Cromossomos Humanos Par 7 , Trissomia/diagnóstico , Adulto , Células Cultivadas , Cromossomos Humanos Par 20/genética , Feminino , Humanos , Mosaicismo , Gravidez , Trissomia/genética
18.
Leukemia ; 34(9): 2441-2450, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32066866

RESUMO

Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequency between the two groups. Patients harbouring ≥2 mutations had a worse outcome than patients with <2 or no mutations (leukaemic transformation at 24 months, 38% and 20%, respectively, p = 0.044). Untreated patients with del(7q) had better overall survival (OS) compared with -7 (median OS, 34 vs 17 months, p = 0.034). In multivariable analysis, blast count, TP53 mutations and number of mutations were independent predictors of OS, whereas the cytogenetic subgroups did not retain prognostic relevance. This study highlights the importance of mutational analysis in terms of prognosis in MDS patients with isolated -7 or del(7q).


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 7 , Mutação , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Prognóstico , Análise de Sobrevida
19.
Ann Hematol ; 99(3): 527-537, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989250

RESUMO

Azacitidine (AZA) is a DNA hypomethylation agent administered in myeloid neoplasms; however, there is still a lack of established predictors of response. We studied 113 patients with myelodysplastic syndromes (n = 85) or acute myeloid leukemia (n = 28) who received AZA to assess the predictive value on response of clinical features, cytogenetics, and molecular markers. Overall, 46 patients (41%) responded to AZA. Platelet doubling after the first AZA cycle was associated with a better response (68% vs. 32% responders, P = 0.041). Co-occurrence of chromosome 7 abnormalities and 17p deletion was associated with a worse response (P = 0.039). Pre-treatment genetic mutations were detected in 98 patients (87%) and methylation of CDKN2B and DLC-1 promoters were detected in 50 (44%) and 37 patients (33%), respectively. Patients with SF3B1 mutations showed a better response to AZA (68% vs. 35% responders, P = 0.008). In contrast, subjects with mutations in transcription factors (RUNX1, SETBP1, NPM1) showed a worse response (20% vs. 47% responders, P = 0.014). DLC-1 methylation pre-treatment was associated with poor clinical features and its reduction post-treatment resulted in a better response to AZA in MDS patients (P = 0.037). In conclusion, we have identified several predictors of response to AZA that could help select the best candidates for this treatment.


Assuntos
Azacitidina/administração & dosagem , Inibidor de Quinase Dependente de Ciclina p15 , Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias , Proteínas Ativadoras de GTPase , Síndromes Mielodisplásicas , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor , Idoso , Idoso de 80 Anos ou mais , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 7/metabolismo , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Intervalo Livre de Doença , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
20.
Cancer Sci ; 111(2): 343-355, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31758608

RESUMO

Chromosome 7q (Ch.7q) is clonally amplified in colorectal cancer (CRC). We aimed to identify oncogenes on Ch.7q that are overexpressed through DNA copy number amplification and determine the biological and clinical significance of these oncogenes in CRC. We identified general transcription factor 2I repeat domain-containing protein 1 (GTF2IRD1) as a potential oncogene using a CRC dataset from The Cancer Genome Atlas with a bioinformatics approach. We measured the expression of GTF2IRD1 in 98 patients with CRC using immunohistochemistry and RT-quantitative PCR (RT-qPCR). The biological effects of GTF2IRD1 expression were explored by gene set enrichment analysis (GSEA). Next, we undertook in vitro cell proliferation and cell cycle assays using siGTF2IRD1-transfected CRC cells. We further investigated the oncogenic mechanisms through which GTF2IRD1 promoted CRC progression. Finally, we assessed the clinical significance of GTF2IRD1 expression by RT-qPCR. GTF2IRD1 was overexpressed in tumor cells and liver metastatic lesions. The GSEA revealed a positive correlation between GTF2IRD1 expression and cell cycle progression-related genes. GTF2IRD1 knockdown inhibited cell proliferation and induced cell cycle arrest in Smad4-mutated CRC. GTF2IRD1 downregulated the expression of the gene encoding transforming growth factor ß receptor 2 (TGFßR2), a tumor-suppressor gene in Smad4-mutated CRC. On multivariate analysis, high GTF2IRD1 expression was an independent poor prognostic factor. Clinicopathological analysis showed that GTF2IRD1 expression was positively correlated with liver metastasis. In conclusion, GTF2IRD1 promoted CRC progression by downregulating TGFßR2 and could be a prognostic biomarker on Ch.7q in CRC. GTF2IRD1 could also be a novel oncogene in CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Transativadores/genética , Transativadores/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Cromossomos Humanos Par 7/genética , Neoplasias Colorretais/metabolismo , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Prognóstico , Regulação para Cima
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