Asunto(s)
Amidohidrolasas/deficiencia , Emparejamiento Base/genética , Enfermedad de Canavan/genética , Cromosomas Humanos Par 17/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Polimorfismo de Nucleótido Simple/genética , Eliminación de Secuencia/genética , Alelos , Amidohidrolasas/genética , Enfermedad de Canavan/enzimología , Niño , Exones/genética , Homocigoto , Humanos , Masculino , Reacción en Cadena de la PolimerasaAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 14 , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/genética , Factor 3 Asociado a Receptor de TNF/genética , Animales , Humanos , Leucemia Linfocítica Crónica de Células B/fisiopatología , Linfoma de Células B/fisiopatologíaRESUMEN
To determine the pattern of genetic alterations in primary central nervous system lymphomas (PCNSL), 19 PCNSL were studied by high-density single-nucleotide polymorphism arrays. Recurrent losses involved 6p21.32, 6q21, 8q12-12.2, 9p21.3, 3p14.2, 4q35.2, 10q23.21 and 12p13.2, whereas gains involved 18q21-23, 19q13.31, 19q13.43 and the entire chromosomes X and 12. Partial uniparental disomies (pUPDs) were identified in 6p and 9p21.3. These genomic alterations affected the HLA locus, the CDKN2A/p16, CDKN2B/p15 and MTAP, as well as the PRDM1, FAS, MALT1, and BCL2 genes. Increased methylation values of the CDKN2A/p16 promoter region were detected in 75% (6/8) PCNSL. Gene expression profiling showed 4/21 (20%) minimal common regions of imbalances to be associated with a differential mRNA expression affecting the FAS, STAT6, CD27, ARHGEF6 and SEPT6 genes. Collectively, this study unraveled novel genomic imbalances and pUPD with a high resolution in PCNSL and identified target genes of potential relevance in the pathogenesis of this lymphoma entity.
Asunto(s)
Neoplasias Encefálicas/genética , Aberraciones Cromosómicas , Cromosomas Humanos/genética , Disomía Uniparental , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Metilación de ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple/genéticaAsunto(s)
Inversión Cromosómica , Proteínas de Unión al ADN/genética , Leucemia-Linfoma de Células T del Adulto/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Adolescente , Cromosomas Humanos Par 11 , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Neoplasias Primarias Secundarias/genética , Proteínas de Fusión Oncogénica , TransactivadoresRESUMEN
The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.
Asunto(s)
Leucemia de Células B/genética , Linfoma de Células B/genética , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción/genética , Translocación Genética , Adulto , Anciano , Proteínas del Linfoma 3 de Células B , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 19 , Análisis Citogenético , Femenino , Reordenamiento Génico , Genes de Inmunoglobulinas , Histocitoquímica , Humanos , Hibridación Fluorescente in Situ , Leucemia de Células B/clasificación , Leucemia de Células B/patología , Linfoma de Células B/clasificación , Linfoma de Células B/patología , Masculino , Persona de Mediana EdadAsunto(s)
Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfoma de Células B/genética , Neoplasias del Mediastino/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Núcleo Celular/metabolismo , Humanos , Linfoma de Células B/metabolismo , Linfoma de Células B/fisiopatología , Neoplasias del Mediastino/metabolismo , Neoplasias del Mediastino/fisiopatología , Proto-Oncogenes Mas , Proteínas RepresorasAsunto(s)
Clatrina/genética , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/genética , Recurrencia Local de Neoplasia/genética , Proteínas Tirosina Quinasas/genética , Adolescente , Quinasa de Linfoma Anaplásico , Niño , Clatrina/metabolismo , Femenino , Humanos , Masculino , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas ReceptorasRESUMEN
Chromosomal translocations affecting the IGH locus and various oncogene loci are recurrent in many types of systemic B-cell lymphomas. Hardly any data exist, however, on such translocations in primary cutaneous B-cell lymphomas (PCBCL). Here, a series of 29 PCBCL was investigated by interphase fluorescence in situ hybridization with probes for the IGH, MYC, BCL6, and MLT1 loci. None of the six follicle center cell lymphomas and nine marginal zone lymphomas showed evidence for any translocation affecting these loci. In contrast, 11 of 14 large B-cell lymphomas of the leg harbored breakpoints in at least one of the loci. Translocations involving the MYC locus were detected in six cases, five of them derived from a MYC/IGH juxtaposition and one from a translocation involving a non-IG gene partner. Rearrangements of the BCL6 locus were detected in five B-cell lymphomas of the leg, and involved IGH (two cases), IGL (one case), and non-IG genes (two cases). This study shows that large B-cell lymphomas of the leg display a pattern of chromosomal translocations similar to their systemic counterparts whereas primary cutaneous follicle center cell lymphomas and marginal zone lymphomas lack these typical chromosomal translocations.
Asunto(s)
Proteínas de Unión al ADN/genética , Genes myc , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células B de la Zona Marginal , Linfoma de Células B/genética , Proteínas de Neoplasias , Proteínas/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias Cutáneas/genética , Factores de Transcripción/genética , Translocación Genética , Adulto , Anciano , Anciano de 80 o más Años , Caspasas , Femenino , Humanos , Inmunoglobulinas/genética , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Proteínas Proto-Oncogénicas c-bcl-6RESUMEN
Tumor cell metaphases of classical Hodgkin's lymphoma (cHL) characteristically display highly rearranged karyotypes with chromosome numbers in the hyperploid range and marked intraclonal variability. The causes of this cytogenetic pattern remain largely unknown. An unusual type of chromosomal abnormality coined as segmental chromosomal aberration (SCA) has been recurrently observed in HL cell lines and was suggested to be associated with ribosomal DNA (rDNA) rearrangements. Moreover, centrosome abnormalities provoking deficient chromosome segregation have been reported in many solid tumors and also in cHL cell lines. Whether SCA, rDNA rearrangements or centrosome abnormalities also occur in primary cHL is not yet known. Thus, we performed extensive molecular cytogenetic and immunohistological studies in two cHL cases. Both cases presented SCA associated with genomic gains of the REL and JAK2 loci, respectively. The SCA involving JAK2 was associated with rDNA rearrangements. The absolute centrosome size of HRS cells in both cases was significantly larger than in non-HRS cells, but the relative centrosome size of HRS cells corrected for nuclear size was in the same range as that of the non-neoplastic cells. These findings demonstrate that the various mechanisms associated with chromosomal instability warrant a more detailed characterization in cHL.
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Centrosoma/patología , Aberraciones Cromosómicas/clasificación , Enfermedad de Hodgkin/genética , Células de Reed-Sternberg/patología , Adulto , Mapeo Cromosómico , Enfermedad de Hodgkin/patología , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana EdadRESUMEN
Chromosomal aberrations with breakpoints in T-cell receptor (TCR) gene loci are recurrent in several T-cell malignancies. Although the importance of interphase cytogenetics has been extensively shown in B-cell lymphomas, hardly any molecular cytogenetic tools are available for recurrent changes in T-cell disorders. Thus, we have established fluorescence in situ hybridization (FISH)-based break-apart assays for the TCRA/D (14q11), TCRB (7q34) and TCRG (7p14) genes and the TCL cluster (14q32). The assays were validated in normal controls as well as in 43 T-cell malignancies with cytogenetically proven 14q11, 7q34-35 or 7p13-21 aberrations. Breakpoints in TCRA/D, TCRB and TCRG could be diagnosed by these assays in 32/33 T-cell neoplasms with chromosome 14q11, 3/6 with 7q34-35 and 1/7 with 7p13-21 alterations, respectively. Application of the new FISH assays to a series of 24 angioimmunoblastic and 12 cutaneous T-cell lymphomas confirmed the cytogenetic evidence of lack of breakpoints in the TCRA/D or TCRB locus. Simultaneous detection of TCRA/D or TCRB breaks was achieved in a multicolor approach, which was further combined with detection of the T-cell-specific CD3 antigen in a multicolor FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasm) assay. These new FISH and FICTION assays provide sensitive, rapid and accurate tools for the diagnosis and biological characterization of T-cell malignancies.
Asunto(s)
Rotura Cromosómica , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 7/genética , Leucemia de Células T/genética , Linfoma de Células T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Adolescente , Adulto , Anciano , Preescolar , Inversión Cromosómica , Pintura Cromosómica/métodos , Reacciones Falso Positivas , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Micosis Fungoide/genética , Eliminación de Secuencia , Síndrome de Sézary/genética , Translocación GenéticaRESUMEN
We describe a patient initially diagnosed with a chronic myeloproliferative disorder in the accelerated phase. Cytogenetic analysis showed the presence of two independent clones. One clone contained a typical Philadelphia (Ph) chromosome due to t(9;22)(q34;q11), as the sole abnormality which was proven molecularly to result in the b2a2-BCR/ABL fusion. The other clone displayed a complex karyotype with several structural and numerical aberrations including trisomy 11 and 22 but lacking a t(9;22) or any other structural abnormalities involving chromosomes 9 and 22. Fluorescence in situ hybridization demonstrated that the t(9;22) was present only in cells with two copies of chromosomes 11 and 22. In contrast, cells with trisomies 11 and 22 lacked evidence for a BCR/ABL fusion. Based on the genetic findings, simultaneous chronic and acute myelocytic leukemias were diagnosed rather than a blastic phase of a chronic myelocytic leukemia.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Anciano , Médula Ósea/fisiología , Cromosomas Humanos , Análisis Citogenético , Diagnóstico Diferencial , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Cromosoma Filadelfia , Translocación GenéticaRESUMEN
The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is a rare but recurrent chromosomal aberration in B-cell malignancies. Hitherto, juxtaposition of BCL11A and IGH has only been described in B-cell chronic lymphocytic leukemia (B-CLL) and immunocytoma. As subgroups of B-CLL can be distinguished by the pattern of somatic mutation of immunoglobulin variable (V) genes we investigated four lymphomas with IGH/BCL11A involvement for IGH hypermutation. Clonal V(H) gene rearrangements were amplified; in all four cases, sequencing of the amplificates revealed the rearranged V(H) genes to lack somatic mutations. These results suggest that t(2;14)(p13;q32.3) is associated with a subset of B-CLL/immunocytoma characterized by non-mutated IG genes deriving from pre-germinal center B cells. As the translocations in both informative cases are targeted to the switch regions of the IGG2 gene, which is mainly used in T cell-independent immune responses, these translocations presumably occurred in activated B cells in the course of T cell-independent immune responses outside the germinal center.
Asunto(s)
Proteínas Portadoras , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 2 , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/genética , Mutación , Proteínas de Neoplasias/genética , Proteínas Nucleares , Translocación Genética , Genes de Inmunoglobulinas , Humanos , Región de Cambio de la Inmunoglobulina , Región Variable de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/clasificación , Leucemia Linfocítica Crónica de Células B/diagnóstico , Linfoma de Células B/diagnóstico , Proteínas Represoras , Análisis de Secuencia de ADNRESUMEN
We describe the structure, genomic organization, and some transcription features of a human brain-specific gene previously localized to the genomic region involved in temporal lobe epilepsy and spastic paraplegia on chromosome 10q24. The gene, which consists of six exons disseminated over 16 kb of genomic DNA, is highly homologous to the porcine tmp83.5 gene and encodes a putative transmembrane protein of 141 amino acids. Unlike its porcine homolog, from which two mRNAs with different 5'-sequences are transcribed, the human gene apparently encodes three mRNA species with 3'-untranslated regions of different sizes. Mutation analysis of its coding sequence in families affected with temporal lobe epilepsy or spastic paraplegia linked to 10q24 do not support the involvement of this gene in either diseases.
Asunto(s)
Encéfalo/metabolismo , Cromosomas Humanos Par 10/genética , Epilepsia del Lóbulo Temporal/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/aislamiento & purificación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/aislamiento & purificación , Paraplejía/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , ADN Complementario/química , ADN Complementario/genética , Exones , Expresión Génica , Genes/genética , Humanos , Intrones , Datos de Secuencia Molecular , Mutación , Proteínas de la Mielina , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , PorcinosRESUMEN
Many malignancies of mature B cells are characterized by chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus on chromosome 14q32.3 and result in deregulated expression of the translocated oncogene. t(2;14)(p13;q32.3) is a rare event in B-cell malignancies. In contrast, gains and amplifications of the same region of chromosome 2p13 have been reported in 20% of extranodal B-cell non-Hodgkin lymphomas (B-NHL), in follicular and mediastinal B-NHL, and in Hodgkin disease (HD). It has been suggested that REL, an NF-kappaB gene family member, mapping within the amplified region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krüppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14)(p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene (BCL11B) on chromosome 14q32.1. BCL11A coamplified with REL in B-NHL cases and HD lymphoma cell lines with gains and amplifications of 2p13, suggesting that BCL11A may be involved in lymphoid malignancies through either chromosomal translocation or amplification.
Asunto(s)
Proteínas Portadoras , Leucemia/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares , Secuencia de Aminoácidos , Animales , Northern Blotting , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 2 , Clonación Molecular , ADN Complementario/química , Femenino , Expresión Génica , Enfermedad de Hodgkin/genética , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Linfoma no Hodgkin/genética , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas de Neoplasias/química , ARN/análisis , Proteínas Represoras , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Translocación Genética , Células Tumorales Cultivadas , Dedos de ZincRESUMEN
Chromosomal translocation t(6;14)(p21.1;q32.3) has been reported as a rare but recurrent event not only in myeloma and plasma cell leukemia but also in diffuse large B-cell non-Hodgkin lymphoma (B-NHL) (diffuse large B-cell lymphoma [DLBCL]) and splenic lymphoma with villous lymphocytes (SLVL); however, the nature of the target gene(s) has not been determined. This study identified t(6;14)(p21.1;q32.3) in 3 cases of transformed extranodal marginal zone B-NHL, in 1 case of SLVL, and in 1 case of a low-grade B-cell lymphoproliferative disorder. In a sixth case, a CD5(+) DLBCL, the translocation was identified by molecular cloning in the absence of cytogenetically detectable change. Two chromosomal translocation breakpoints were cloned by using long-distance inverse polymerase chain reaction methods. Comparison with the genomic sequence for chromosome 6p21.1 showed breakpoints approximately 59 and 73.5 kilobases 5' of the cyclin D3 (CCND3) gene with no other identifiable transcribed sequences in the intervening region. Although Southern blotting with derived genomic 6p21.1 probes failed to detect other rearrangements, fluorescent in situ hybridization assays, using BAC (bacterial artificial chromosome) clones spanning and flanking the CCND3 locus, along with probes for IGH confirmed localization of 6p21.1 breakpoints within the same region, as well as fusion of the CCND3 and IGH loci. Furthermore, in all cases, high-level expression of CCND3 was demonstrated at RNA and/or protein levels by Northern and Western blotting and by immunohistochemistry. These data implicate CCND3 as a dominant oncogene in the pathogenesis and transformation in several histologic subtypes of mature B-cell malignancies with t(6;14)(p21.1;q32.3) and suggest that CCND3 overexpression seen in about 10% of DLBCL cases may have a genetic basis.
Asunto(s)
Cromosomas Humanos Par 14 , Cromosomas Humanos Par 6 , Ciclinas/genética , Linfoma de Células B/genética , Trastornos Linfoproliferativos/genética , Translocación Genética/genética , Adulto , Anciano , Linfocitos B/química , Linfocitos B/patología , Linfocitos B/ultraestructura , Secuencia de Bases , Rotura Cromosómica/genética , Clonación Molecular , Ciclina D3 , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B/química , Linfoma de Células B/patología , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
Structural alterations in 3q27 affecting the BCL6 locus are among the most frequent changes in B-NHL. The aim of the present study was to establish an interphase-FISH assay for the detection of all diverse BCL6 translocations in B-NHL. Two different approaches were tested, one using a PAC-clone spanning the major breakpoint region (MBR) of BCL6 (span-assay), and another using two BAC clones flanking the MBR (flank-assay). Interphase FISH with the span-assay detected the various BCL6 translocations in seven B-NHL cell lines. The dual-color flank-assay was evaluated in two laboratories independently: in normal controls, the cutoff level for false-positive signals was 2.6%, whereas the cutoff level for false-negatives in the seven cell lines was 7.5%. To test the feasibility of the FISH strategies, 30 samples from patients with B-NHL with cytogenetic abnormalities of 3q27 were evaluated with both assays. In 21 cases, the span-assay indicated a BCL6 rearrangement. In 18 of the 21 cases, the dual-color flank-assay confirmed the translocation including 12 different partner chromosomal loci. The three false-positive cases detected with the span-assay showed trisomy of chromosome 3 by cytogenetic analyses, and they were correctly classified as non-rearranged with the flank-assay. In summary, our FISH strategy using two differently labeled flanking BCL6 BAC probes provides a robust, sensitive, and reproducible method for the detection of common and uncommon abnormalities of BCL6 gene in interphase nuclei. The routine application of this assay to patients with B-NHL will allow the assessment of the diagnostic and prognostic significance of BCL6 rearrangements.
Asunto(s)
Cromosomas Humanos Par 3 , Linfoma de Células B/genética , Translocación Genética , Secuencia de Bases , Bandeo Cromosómico , Femenino , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Datos de Secuencia MolecularRESUMEN
The t(10;14)(q24;q11) and its variant t(7;10)(q35;q24), which are recurrent in acute T-cell leukemia, lead to activation of the HOX11/TCL3-gene in chromosomal region 10q24 by juxtaposing this gene to one of the T-cell receptor loci. In the present study, we established a diagnostic assay for detecting these translocations by interphase fluorescence in situ hybridization (FISH). BAC clones flanking the HOX11/TCL3-locus were obtained from a fingerprinted BAC-contig of chromosomal region 10q24. BAC clones located proximal and distal of the HOX11/TCL3-locus were differently labeled and applied to interphase-FISH in seven normal controls and eight T-cell neoplasms with t(10;14)(q24;q11) or t(7;10)(q35;q24). In over 1600 nuclei of controls, a considerable split defined as separation of each one signal for the proximal and distal probe by more than three times the signal diameter was observed in only one cell. In contrast, all T-cell neoplasms with t(10;14) or t(7;10) contained at least 47% of nuclei with a signal split indicating a breakpoint in the HOX11/TCL3-locus. Thus, the established double-color FISH approach provides a new reliable and routinely applicable tool for diagnosing breakpoints in the HOX11/TCL3-locus.
Asunto(s)
Cromosomas Humanos Par 10 , Proteínas de Homeodominio/genética , Hibridación Fluorescente in Situ , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas Oncogénicas/genética , Translocación Genética , Adulto , Niño , Preescolar , Mapeo Cromosómico , Femenino , Humanos , Interfase , Masculino , Persona de Mediana Edad , Proteínas Proto-OncogénicasRESUMEN
A patient is described with myelodysplastic syndrome (MDS) progressing to acute myeloid leukemia (AML) FAB M4. Cytogenetic analysis revealed an unusual rearrangement between chromosomes 9 and 17, leading to a dicentric chromosome with an insertion of material of unknown origin between both chromosomes. By fluorescence in situ hybridization (FISH), the insertion was shown to be an amplification of part of 17q, involving ERBB2, RARA, and TOP2A genes. The median copy number of ERBB2, RARA, and TOP2A genes in the tumor cells was six (range: 4--10). Only one copy of the MPO gene at 17q21.3 was detected, suggesting a deletion of the telomeric part of 17q. To our knowledge, this is the first report of a 17q amplification in AML.