RESUMO
STUDY QUESTION: What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? SUMMARY ANSWER: Minimal disseminated disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. WHAT IS KNOWN ALREADY: In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. STUDY DESIGN, SIZE, DURATION: The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MAIN RESULTS AND THE ROLE OF CHANCE: MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. LIMITATIONS, REASONS FOR CAUTION: Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any disseminated disease. Moreover, molecular markers are not readily available for all types of tumors. WIDER IMPLICATIONS OF THE FINDINGS: These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Télévie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests.
Assuntos
Neoplasias Ósseas/patologia , Criopreservação , Preservação da Fertilidade/métodos , Ovário/patologia , Sarcoma/secundário , Adolescente , Adulto , Criança , Feminino , Humanos , Adulto JovemRESUMO
Aneurysmal bone cystic (ABC) lesions can be primary or secondary (to a trauma or a pre-existing benign or malignant tumour). Specific translocations of the USP6 gene are reported in about 70% of primary but never in secondary ABC lesions. We report two cases of ABC lesions in which imbalanced genomic aberrations were detected at initial presentation and showed complex clonal evolution. These demonstrative observations strengthen the guidelines regarding the diagnostic approach when an ABC is suggested by imaging. Biopsy is mandatory including genomic analysis. When a primary ABC is not clearly proven by the initial biopsy, an extensive curettage should be performed, with pathological examination of all removed tissue in order to exclude a secondary ABC. It also illustrates the added value of genomic analyses in the setting of an ABC lesion: complex clonal aberrations argues for a lesion secondary to a malignant proliferation whereas USP6 rearrangement allows the diagnosis of primary ABC.
Assuntos
Cistos Ósseos Aneurismáticos/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas/genética , Ubiquitina Tiolesterase/genética , Adolescente , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/patologia , Cistos Ósseos Aneurismáticos/cirurgia , Feminino , Testes Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Imageamento por Ressonância Magnética , Masculino , RadiografiaRESUMO
BACKGROUND: Oncological care was considerably impacted by the COVID-19 pandemic. Worrisome declines in diagnostic procedures and cancer diagnoses in 2020 have been reported; however, nationwide, population-based evidence is limited. Quantification of the magnitude and distribution of the remaining outstanding diagnoses is likewise lacking. METHODS: Using accelerated delivery of data from pathology laboratories to the Belgian Cancer Registry, we compared the nationwide rates of new diagnoses of invasive cancers in 2020 to 2019. RESULTS: We observed a 44% reduction in total diagnoses of invasive cancers in April 2020 compared with April 2019, coinciding with the first wave of the COVID-19 pandemic. The reduction was largest in older patients and for skin cancers (melanoma and nonmelanoma). Reductions in diagnosis were less pronounced among children and adolescents (0-19 years). A smaller decline was observed for most cancers with typically poorer prognosis or obvious symptoms, including some hematological malignancies, lung, and pancreatic cancer. Suspension of organized population screening programs was reflected in a strong decline in diagnosis in the screening age groups for female breast cancer (56%) and for colorectal cancer in both men (49%) and women (60%). The number of diagnoses began to increase from the end of April and stabilized at the beginning of June at or just above 2019 levels. There has yet to be a complete recovery in cancer diagnoses, with an estimated 6%, or â¼4000 diagnoses, still outstanding for all of 2020. Among solid tumors, head and neck cancers have the largest remaining year-over-year decrease in diagnoses at 14%. CONCLUSION: These results add to the evidence of a profound impact of the COVID-19 pandemic on oncological care and identify groups at risk for continuing diagnostic delays. These data should stimulate health care providers worldwide to facilitate targeted, accessible, and efficient procedures for detection of cancers affected by this delay.
Assuntos
Neoplasias da Mama , COVID-19 , Adolescente , Idoso , Bélgica/epidemiologia , Criança , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMO
The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3' portion of JAK2 to the 5' region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line.
Assuntos
Leucemia-Linfoma de Células T do Adulto/metabolismo , Proteínas do Leite , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Sequência de Aminoácidos , Animais , Sequência de Bases , Biopolímeros , Divisão Celular , Linhagem Celular , Pré-Escolar , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Ativação Enzimática , Humanos , Interleucina-3/fisiologia , Janus Quinase 2 , Leucemia-Linfoma de Células T do Adulto/genética , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas de Fusão Oncogênica/química , Proteínas de Fusão Oncogênica/genética , Fosforilação , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-ets , Fator de Transcrição STAT5 , Transdução de Sinais , Transativadores/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção , Translocação Genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
We report on an acute myeloid leukemia in a neonate whose mother was exposed to diethylstilboestrol in utero. The newborn presented with leukemia cutis, hemorrhagic skin lesions, hyperleucocytosis and disseminated intravascular coagulation. A bone marrow examination confirmed the diagnosis of acute monocytic leukemia with a t(11;19) MLL-ELL fusion transcript. Chemotherapy was initiated but the child developed a bilateral pulmonary infection that led to fatal respiratory distress. This case shows acute myeloid leukemia and the third pediatric leukemia reported after maternal diethylstilboestrol exposure.
Assuntos
Dietilestilbestrol/efeitos adversos , Estrogênios não Esteroides/efeitos adversos , Leucemia Mieloide Aguda/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Infertilidade Feminina/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Mães , Proteína de Leucina Linfoide-Mieloide , Proteínas de Fusão Oncogênica , Linhagem , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
Assuntos
Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Adolescente , Adulto , Criança , Deleção Cromossômica , Inversão Cromossômica , Feminino , Rearranjo Gênico do Linfócito T , Proteínas Homeobox A10 , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Masculino , Pessoa de Meia-Idade , Receptor Notch1/genética , Ativação Transcricional , Translocação GenéticaRESUMO
The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.
Assuntos
Neoplasias Hematológicas/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Translocação Genética/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Citogenética , Feminino , França , Proteínas de Homeodomínio/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-Idade , Receptores Citoplasmáticos e Nucleares/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Sociedades MédicasRESUMO
The TEL/ETV6 gene is located at 12p13 and is frequently involved in chromosomal translocations in human malignancies usually resulting in the expression of fusion proteins between the amino terminal part of TEL, and either unrelated transcription factors or protein tyrosine kinases. We report here a novel gene named TELB which is located on human chromosomal band 6p21 and encodes a protein highly related to TEL. TELB is widely expressed in different tissues and, similarly to TEL encodes a sequence-specific transcriptional repressor.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Drosophila , Genes , Leucemia/genética , Proteínas Proto-Oncogênicas , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Linfoma de Burkitt/genética , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 6/ultraestrutura , Subunidade alfa 2 de Fator de Ligação ao Core , DNA Complementar/genética , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/biossíntese , Drosophila melanogaster/genética , Éxons/genética , Etiquetas de Sequências Expressas , Proteínas do Olho/genética , Regulação Leucêmica da Expressão Gênica , Células HeLa , Humanos , Dados de Sequência Molecular , Família Multigênica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-ets , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Fatores de Transcrição/biossíntese , Transcrição Gênica , Transfecção , Translocação Genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The predicted product of TEL harbours an amino acid region similar to the ETS DNA binding domain. We now report the isolation of the murine TEL cDNA and the characterization of the human TEL proteins. Human and murine TEL proteins are particularly homologous within their aminoterminal regions and their ETS domains. TEL proteins are nuclear and display specific DNA binding activity toward classical ETS binding sites. In addition, we show that TEL mRNAs initiate translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50 kDa and 57 kDa TEL proteins. In vivo, each of these primary translational products is modified by multiple phosphorylation events.
Assuntos
DNA Complementar/genética , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Animais , Sequência de Bases , Western Blotting , Células COS , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Clonagem Molecular , DNA/metabolismo , DNA Complementar/isolamento & purificação , Proteínas de Ligação a DNA/isolamento & purificação , Humanos , Hibridização in Situ Fluorescente , Leucemia de Células B/genética , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/isolamento & purificação , Fosfoproteínas/isolamento & purificação , Fosforilação , Proteínas Proto-Oncogênicas c-ets , RNA Mensageiro/isolamento & purificação , Fatores de Transcrição/isolamento & purificação , Translocação Genética , Células Tumorais Cultivadas , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Inappropriate activation of Abl family kinases plays a crucial role in different human leukaemias. In addition to the well known oncoproteins p190Bcr-Abl and p210Bcr-Abl, Tel-Abl, a novel fusion protein resulting from a different chromosomal translocation, has recently been described. In this study, the kinase specificities of the Bcr-Abl and Tel-Abl proteins were compared to the physiological Abl family kinases c-Abl and Arg (abl related gene). Using short peptides which correspond to the target epitopes in known substrate proteins of Abl family kinases, we found a higher catalytic promiscuity of Bcr-Abl and Tel-Abl. Similar to Bcr-Abl, Tel-Abl was found in complexes with the adapter protein CRKL. In addition, c-Crk II and CRKL are tyrosine phosphorylated and complexed with numerous other tyrosine phosphorylated proteins in Tel-Abl expressing Ba/F3 cells. GTPase analysis with a Ras-GTP-specific precipitation assay showed constitutive elevation of GTP-loaded Ras in cells expressing the leukaemic Abl proteins. The mitogenic MAPK/Erk kinases as well as Akt/PKB, a kinase implicated to negatively regulate apoptosis, were also constitutively activated by both Bcr-Abl and Tel-Abl. The results indicate that the leukaemic Abl-fusion proteins have catalytic specificities different from the normal kinases c-Abl and Arg and that Tel-Abl is capable to activate at least some pathways which are also upregulated by Bcr-Abl.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Sistema de Sinalização das MAP Quinases , Proteínas de Fusão Oncogênica/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteínas Serina-Treonina Quinases , Células 3T3 , Sequência de Aminoácidos , Animais , Catálise , Linhagem Celular , Epitopos/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Guanosina Trifosfato/fisiologia , Células-Tronco Hematopoéticas , Humanos , Substâncias Macromoleculares , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-crk , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Especificidade por Substrato , Translocação GenéticaRESUMO
Chromosomal translocations involving the human 12p13 band frequently affect the TEL gene, usually resulting in gene fusion between TEL and genes encoding proteins of various types. The most frequent 12p13 translocation is the t(12;21)(p13;q22), which recombines TEL with the AML1 gene on chromosome 21 and is frequently associated with deletion of the untranslocated TEL allele. Using antisera against different parts of TEL and against the AML1 proteins, we undertook Western blot and immunofluorescence analyses of leukemic samples with and without 12p13 abnormalities. In t(12;21) samples, TEL-AML1 was detected as several protein species in the nuclei, whereas the AML1-TEL protein, was inconsistently expressed. AML1 was found to be expressed but no normal TEL proteins were detected. A survey of the TEL proteins in a panel of human leukemic samples without t(12;21) revealed a variation in the ratio of TEL protein isoforms. We also analysed a leukemic cell line bearing a t(12;22)(p13;q11) that was found to affect the 5' untranslated (UT) region of TEL and to be associated with inactivation of the untranslocated TEL allele. No MN1-TEL fusion could be detected upon RT-PCR analysis, in contrast to the previously investigated t(12;22). Strikingly, extremely low levels of apparently normal TEL proteins, expressed from the translocated allele, were detected by Western blot analysis. These results suggest that the level of TEL expression can be important for leukemogenesis.
Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Proteínas de Ligação a DNA/metabolismo , Leucemia Mielomonocítica Aguda/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Fatores de Transcrição/metabolismo , Adulto , Animais , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core , Células HL-60 , Células HeLa , Humanos , Isomerismo , Leucemia Mielomonocítica Aguda/patologia , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Proto-Oncogênicas c-ets , Coelhos , Frações Subcelulares , Translocação Genética , Células Tumorais Cultivadas , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Translocation t(12;21) has been described as a nonrandom event in acute lymphoblastic leukemia (ALL) in patients with deletion of the short arm of chromosome 12, using fluorescence in situ hybridization techniques. Extensive FISH experiments were performed in order to re-examine the short arm of chromosome 12 in three children with ALL, previously shown to have t(12;21). It was shown that the t(12;21) is undetectable by routine R-banding technique and that the translocated 12 looks like a cytogenetically normal chromosome 12 in the three patients. Partial 12p deletion involving the TEL locus was shown to be interstitial in one patient with 12p- by using cosmid and YAC probes. In the second patient, the 12p- chromosome was secondary to the translocation since it was observed in about one half of the metaphases analyzed with FISH. In the third patient, the region of TEL usually rearranged in the t(12;21) displayed a germline pattern by Southern blotting, at diagnosis and in relapse. A few metaphases showed associated 12p- by standard cytogenetics, only in relapse. Thus we conclude that the TEL allele not involved in t(12;21) is inconstantly lost in patients with this subtype of ALL and occurs on the 12p- chromosome. These data question the status of tumor suppressor gene hypothesized for TEL.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Southern Blotting , Criança , Humanos , Hibridização in Situ FluorescenteRESUMO
The TEL gene is involved in several chromosomal abnormalities of human hematopoietic malignancies. The chromosome 12 breakpoints frequently lie within the fifth intron of the gene, particularly in the most frequent translocation involving TEL, the t(12;21)(p13;q22). In order to search for a peculiar mechanism involved in the genesis of these translocations, we have established the sequence of two t(12;21) and a t(9;12)(q24;p13) breakpoints. Our data do not reveal the involvement of VDJ recombinase activity or Alu sequences but favor the occurrence of staggered breaks and DNA repair activity in the genesis of these translocations.
Assuntos
Linfoma de Burkitt/genética , Quebra Cromossômica/genética , Cromossomos Humanos Par 12/genética , Proteínas de Ligação a DNA/genética , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Translocação Genética/genética , Alelos , Elementos Alu/genética , Sequência de Bases , Criança , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 9/genética , Análise Mutacional de DNA , DNA Nucleotidiltransferases/metabolismo , Reparo do DNA/genética , Éxons/genética , Humanos , Íntrons/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Mapeamento Físico do Cromossomo , Proteínas Proto-Oncogênicas c-ets , Recidiva , VDJ Recombinases , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
BACKGROUND: Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm arising from plasma cells. SEP mostly occurs in the upper respiratory tract. Thyroid gland is rarely affected (<78 cases). METHODS/RESULTS: We describe the case of a 78-year-old woman presenting a rapidly enlarging palpable thyroid mass. Neck computed tomography scan showed enlargement of both thyroid lobes. Laboratory tests were normal, including serum protein level with no monoclonal gamma globulin peak. Cytology was suspicious for lymphoma. Biopsy showed an infiltrating neoplasm composed of atypical tumor cells with abundant cytoplasm and eccentric nuclei. These revealed diffuse immunoreactivity for CD138 and predominant staining for immunoglobulin kappa light chains. Clinical workup for multiple myeloma was negative. CONCLUSIONS: SEP should be considered in the differential diagnosis of a rapidly enlarging thyroid nodule and be distinguished from involvement of thyroid in multiple myeloma, mucosa-associated lymphoid tissue lymphoma, plasma cell granuloma and medullary carcinoma. Clinical correlation and immunohistochemistry are crucial in avoiding pitfalls.
Assuntos
Plasmocitoma/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Carcinoma Neuroendócrino , Diagnóstico Diferencial , Feminino , Humanos , Plasmócitos/patologia , Plasmocitoma/sangue , Plasmocitoma/química , Plasmocitoma/diagnóstico , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
Inactivation of the non translocated TEL/ETV6 gene is commonly associated with translocation (12;21) of acute lymphoblastic leukemia (ALL). Translocations involving the short arm of chromosome 12 were analysed in two children with t(12;21) ALL. Fluorescence in situ hybridation studies showed that these associated translocations resulted in loss of TEL/ETV6. While hybridization with a YAC probe covering TEL/ETV6 was positive in one patient, analysis with cosmid probes covering the gene demonstrated that the gene was in fact deleted. It is concluded that deletions involving TEL/ETV6 can remain undetected by FISH using only YAC probes.
Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Proteínas de Ligação a DNA/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Translocação Genética , Adolescente , Pré-Escolar , Feminino , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Proteínas Proto-Oncogênicas c-ets , Recidiva , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
The translocation t(12;21)(p13;q22) is a frequent nonrandom rearrangement of B-cell lineage childhood acute lymphoblastic leukemia (ALL) which fuses the TEL and AML1 genes, normally localized to 12p13 and 21q22, respectively. The crucial chimeric gene, TEL-AML1, is transcribed from the der(21) and encodes the 336 NH2 aminoacics of TEL fused to the majority of the AML1 protein. The t(12;21) is very often associated with loss of the normal, untranslocated TEL allele. These various aspects are presented here.
Assuntos
Linfoma de Burkitt/genética , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Humanos , Biologia MolecularRESUMO
Trisomy 14 as single karyotype aberration was detected in three patients, two with acute myeloblastic leukemia, AML-M2 type, and one with aplastic anemia. These new observations and the 28 previously reported cases confirm that trisomy 14 is a primary non random change, mostly confined to myeloid disorders.
Assuntos
Anemia Aplástica/genética , Cromossomos Humanos Par 14 , Leucemia Mieloide Aguda/genética , Trissomia , Adulto , Idoso , Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Doenças da Medula Óssea/genética , Evolução Fatal , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genéticaRESUMO
Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P=0.030), 2.5 (P=0.015) and 4.0 (P=0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.
Assuntos
Aberrações Cromossômicas , Linfoma de Células B/genética , Adolescente , Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células B/epidemiologia , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
Episomes with the NUP214-ABL1 fusion gene have been observed in 6% of T-ALL. In this multicentric study we collected 27 cases of NUP214-ABL1-positive T-ALL. Median age was 15 years with male predominance. Outcome was poor in 12 patients. An associated abnormality involving TLX1 or TLX3 was found in all investigated cases. Fluorescent in situ hybridization revealed a heterogeneous pattern of NUP214-ABL1 amplification. Multiple episomes carrying the fusion were detected in 24 patients. Episomes were observed in a significant number of nuclei in 18 cases, but in only 1-5% of nuclei in 6. In addition, intrachromosomal amplification (small hsr) was identified either as the only change or in association with episomes in four cases and two T-ALL cell lines (PEER and ALL-SIL). One case showed insertion of apparently non-amplified NUP214-ABL1 sequences at 14q12. The amplified sequences were analyzed using array-based CGH.These findings confirm that the NUP214-ABL1 gene requires amplification for oncogenicity; it is part of a multistep process of leukemogenesis; and it can be a late event present only in subpopulations. Data also provide in vivo evidence for a model of episome formation, amplification and optional reintegration into the genome. Implications for the use of kinase inhibitors are discussed.
Assuntos
Amplificação de Genes , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas de Fusão Oncogênica/genética , Adolescente , Adulto , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Proteínas de Homeodomínio/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/etiologia , Masculino , Pessoa de Meia-Idade , Plasmídeos , Proteínas Proto-Oncogênicas/genética , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.