RESUMEN
Structural abnormalities of chromosome 7q have been regularly reported in chronic B-cell lymphoproliferative disorders. They include chromosomal translocations involving 7q21, leading to overexpression of the CDK6 gene. Three different translocations, t(7;14)(q21;q32), t(7;22)(q21;q11), and t(2;7)(p11;q21), leading to the juxtaposition of the CDK6 gene with a immunoglobulin gene enhancer during B-cell differentiation, have been described. In the past 2 years, we identified three patients with lymphoproliferative malignancy associated with a t(2;7)(p11;q21). Fluorescent in situ hybridization using an IGK probe and a library of bacterial artificial chromosome (BAC) clones located in bands 7q21.2 and 7q21.3, containing CDK6, revealed that the telomeric part of the IGK probe was translocated on the der(7) within a 51-kb region upstream of the transcriptional start site of CDK6. A total of 23 patients with indolent B-cell lymphoproliferative disorders and juxtaposition of the IG and CDK6 genes, including 20 with IGK and CDK6 juxtaposition, have been reported thus far. This rearrangement leads to the overexpression of CDK6, which encodes a cyclin-dependent protein kinase involved in cell cycle G1 phase progression and G1/S transition.
Asunto(s)
Linfocitos B/inmunología , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 7 , Trastornos Linfoproliferativos/genética , Translocación Genética , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Trastornos Linfoproliferativos/inmunología , Persona de Mediana EdadRESUMEN
Inv(3)(q21q26)/t(3;3)(q21;q26) is a feature of a distinctive entity of acute myeloid leukemia (AML) associated with normal or elevated platelet count, atypical megakaryocytes and multilineage dysplasia in the bone marrow, as well as minimal to no response to chemotherapy and poor clinical outcome. The presence of an inversion on both chromosome 3s is a rare event, as only eight cases have been reported in the literature. Recently, we identified two patients with AML carrying a double inv(3)(q21q26). Using librairies of bacterial artificial chromosome clones mapping to bands 3q21 and 3q26, we found that the regions in which the breakpoints occurred were different in both patients, but located in the same restricted areas in each patient. Although it cannot be excluded that inversion occurred independently on both chromosome 3s, it is more likely that the presence of a double inv(3) is the result of loss of the normal chromosome 3 followed by a duplication of the inverted chromosome, or segmental loss of heterozygosity followed by a somatic repair mechanism.
Asunto(s)
Inversión Cromosómica/genética , Cromosomas Humanos Par 3/genética , Leucemia Mieloide Aguda/genética , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana EdadRESUMEN
Inv(3)(q21q26)/t(3;3)(q21;q26) is recognized as a distinctive entity of acute myeloid leukemia (AML) with recurrent genetic abnormalities of prognostic significance. It occurs in 1-2.5% of AML and is also observed in myelodysplastic syndromes and in the blastic phase of chronic myeloid leukemia. The molecular consequence of the inv(3)/t(3;3) rearrangements is the juxtaposition of the ribophorin I (RPN1) gene (located in band 3q21) with the ecotropic viral integration site 1 (EVI1) gene (located in band 3q26.2). Following conventional cytogenetics to determine the karyotype, fluorescent in situ hybridization (FISH) with a panel of bacterial artificial chromosome clones was used to map the breakpoints involved in 15 inv(3)/t(3;3). Inv(3) or t(3;3) was the sole karyotypic anomaly in 6 patients, while additional abnormalities were identified in the remaining 9 patients, including 4 with monosomy of chromosome7 (-7) or a deletion of its long arm (7q-). Breakpoints in band 3q21 were distributed in a 235 kb region centromeric to and including the RPN1 locus, while those in band 3q26.2 were scattered in a 900 kb region located on each side of and including the EVI1 locus. In contrast to most of the inversions and translocations associated with AML that lead to fusion genes, inv(3)/t(3;3) does not generate a chimeric gene, but rather induces gene overexpression. The wide dispersion of the breakpoints in bands 3q21 and 3q26 and the heterogeneity of the genomic consequences could explain why the mechanisms leading to leukemogenesis are still poorly understood. Therefore, it is important to further characterize these chromosomal abnormalities by FISH.
Asunto(s)
Rotura Cromosómica , Inversión Cromosómica/genética , Cromosomas Humanos Par 3/genética , Citogenética/métodos , Neoplasias Hematológicas/genética , Hibridación Fluorescente in Situ/métodos , Translocación Genética , Cromosomas Artificiales Bacterianos/genética , Sondas de ADN/metabolismo , Proteínas de Unión al ADN/genética , Femenino , Humanos , Proteína del Locus del Complejo MDS1 y EV11 , Masculino , Persona de Mediana Edad , Proto-Oncogenes/genética , Factores de Transcripción/genéticaRESUMEN
We report here three children with a der(11)t(11;16), two sibs (patients 1 and 2) having inherited a recombinant chromosome from a maternal t(11;16)(q24.3;q23.2) and a third unrelated child with a de novo der(11)t(11;16)(q25;q22.1), leading to partial monosomy 11q and trisomy 16q. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones and array-CGH were performed to determine the breakpoints involved in the familial and the de novo rearrangements. The partial 11 monosomy extended from 11q24.3 to 11qter and measured 6.17-6.21 Mb in Patients 1 and 2 while the size of the partial 11q25->qter monosomy was estimated at 1.97-2.11 Mb for Patient 3. The partial 16 trisomy extended from 16q23.2 to 16qter and measured 8.93-8.95 Mb in Patients 1 and 2 while the size of the partial 16q22.1->qter trisomy was 20.82 Mb for Patient 3. Intraventricular hemorrhage and transitional thrombocytopenia were found in both sibs but not in the third patient. The FLI1 gene, which is the most relevant gene for thrombocytopenia in Jacobsen syndrome, was neither deleted in family A nor in Patient 3. We suggest that a positional effect could affect the FLI1 expression for these two sibs. Deafness of our three patients confirmed the association of this anomaly to 11q monosomy and tended to confirm the hypothetic role of DFNB20 in Jacobsen syndrome hearing loss. Both sibs shared most of the features commonly observed in Jacobsen syndrome, but not the third patient. This confirmed that terminal 11q trisomy spanning 1 to 1.97-2.11 Mb is not associated with a typical Jacobsen syndrome.
Asunto(s)
Rotura Cromosómica , Deleción Cromosómica , Cromosomas Humanos Par 11/genética , Síndrome de Deleción Distal 11q de Jacobsen/genética , Trisomía/genética , Niño , Preescolar , Cromosomas Humanos Par 16/genética , Sordera/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipo , Masculino , Proteína Proto-Oncogénica c-fli-1/genética , Hermanos , Translocación GenéticaAsunto(s)
Células de la Médula Ósea/patología , Trastornos de los Cromosomas/genética , Cromosomas Humanos Par 5/genética , Isocromosomas/genética , Síndromes Mielodisplásicos/genética , Adulto , Células Cultivadas , Bandeo Cromosómico , Humanos , Masculino , Síndromes Mielodisplásicos/patología , Adulto JovenRESUMEN
Cytogenetic abnormalities identified by conventional cytogenetics (CC) have important prognostic and therapeutic roles in myelodysplastic syndromes (MDS). Fluorescence in situ hybridization (FISH) complements CC since it is able to evaluate large numbers of interphase and metaphase nuclei. The question has been raised as to whether interphase FISH in addition to CC is able to imprive the level of detection of del(5q) and del(20q) in MDS. This study performed interphase FISH with 5q and 20q probes in a series of 158 MDS patients with a normal karyotype. No hidden del(5q) or del(20q) was detected. A review of the literature identified 20 patients (1.96%) of 1018 patients (including the current series) and 3 (0.91%) of 331 patients to have a del(5q) or del(20q). Therefore, interphase FISH adds little, if any, improvement to the probability of detecting these deletions. However, interphase FISH is recommended in patients with no cell growth or when fewer than 20 metaphases are available for CC analysis.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 20/genética , Cromosomas Humanos Par 5/genética , Hibridación Fluorescente in Situ , Interfase , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Humanos , Cariotipificación , Síndromes Mielodisplásicos/clasificación , Síndromes Mielodisplásicos/patologíaRESUMEN
We report the case of a 74-year-old man who sought care for de novo myelodysplastic syndrome (RAEB-1). Conventional cytogenetic techniques showed a karyotype with two different deletions of the long arm of chromosome 5 distributed in three clones: 46,XY,del(1)(p34),del(5)(q14q23)[2]/46,XY,del(1)(p34),del(5)(q14q34)[10]/46,idem,inv(5)(q?11q?34)[7]. Precise characterization of the breakpoints, delineation of the deleted regions, identification of the complex intrachromosomal rearrangement of chromosome 5, and sequential accumulation of chromosomal abnormalities were elucidated by several fluorescence in situ hybridization analyses. We also assessed the clinical, biological, and cytogenetic evolution under lenalidomide treatment and after its interruption.
Asunto(s)
Cromosomas Humanos Par 5 , Reordenamiento Génico , Síndromes Mielodisplásicos/genética , Anciano , Bandeo Cromosómico , Mapeo Cromosómico , Cromosomas Artificiales Bacterianos , Citogenética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Lenalidomida , Masculino , Talidomida/análogos & derivados , Talidomida/farmacologíaRESUMEN
The Manila clam Ruditapes philippinarum was introduced to Norway in 1987 and was produced in 2 hatcheries until 1991. Clam seed was planted at 6 sites. Two sites were on the Island of Tysnes, south of Bergen. Surviving adult Manila clams were recovered in 1995 and 1996. In the present study, Manila clams from the original seeding that displayed morphological signs of brown ring disease (BRD) were recovered in June 2003 (n=7) and in June 2004 (n=17). Samples from extrapallial fluid, tissues and haemolymph were inoculated on marine agar. Replicate subcultures on selective media were used to select potential Vibrio tapetis strains, and in total, 190 bacterial strains were isolated. One of these strains clustered within the V tapetis clade and was named NRP 45. DNA:DNA hybridisation with the type strain CECT4600 showed 52.7 and 57.3% DNA:DNA similarity. Hybridisation of NRP 45 and the V tapetis LP2 strain, isolated from corkwing wrasse Symphodus melops, produced 46.6 and 44.4% re-association. Partial gene segments encoding 16S rRNA, gyrase B protein (GyrB) and chaperonin 60 protein (Cpn60) were characterised and compared to CECT 4600. NRP 45 showed 5 differences in the 1416 nucleotides (nt) of the 16S rRNA encoding gene (99.6% similarity), while the GyrB encoding gene had 62 substitutions of 1181 nt compared (94.8% similarity) and the Cpn60 encoding gene had 22 substitutions out of 548 nt compared (96% similarity). This is the first finding of BRD and the first isolation of a V. tapetis-like bacterial strain from a bivalve in Norway.