RESUMEN
Renal clear cell carcinoma (CCRCC) is an aggressive tumor for which new prognostic factors are needed. It has been suggested that CCRCCs co-expressing P53 and MDM2 could represent a special subgroup; therefore the aim of this study was to explore their immunohistochemical features. The material studied consisted of 470 cases of CCRCC. Immunohistochemistry for MDM2, P53, Ki-67, VEGF-A, VEGF-C, VEGF-D, GLUT1, CA9, and CK 7 was performed on tissue microarrays and assessed semi-quantitatively. On average, 6.6% or 5.3% of cases were P53+/MDM2+, depending on the P53 antibody used. The mean percentage of Ki-67 positive cells was 0.6% and p53-positive MDM2-positive cases showed significantly higher expression of Ki-67. The other immunohistochemical parameters studied did not differ between p53-positive MDM2-positive cases and the rest of the subtypes studied. Expression of almost all immunohistochemical markers differed with respect to pT stage; only for CA9 was the difference not significant. Furthermore, almost all immunohistochemical markers studied differed with respect to differences in grade; only for GLUT1 was the difference not significant. Our results suggest that with the exception of Ki-67, there are no significant associations between analyzed markers and the double P53+/MDM2+ phenotype.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/química , Inmunohistoquímica , Neoplasias Renales/química , Proteínas Proto-Oncogénicas c-mdm2/análisis , Proteína p53 Supresora de Tumor/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Fenotipo , Valor Predictivo de las Pruebas , Análisis de Matrices TisularesRESUMEN
Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.
Asunto(s)
Linfoma/clasificación , Linfoma/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Sistema de Registros , Distribución por Sexo , Organización Mundial de la SaludRESUMEN
A case of pregnancy associated extrauterine decidual reaction of great omentum in a 25 year old woman, incidentally discovered during microscopic examination is described with a short review of literature.
Asunto(s)
Coristoma , Decidua , Enfermedades Peritoneales/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Femenino , Humanos , EmbarazoRESUMEN
We describe a child with global developmental delay, prominent metopic suture, trigonocephaly, and cryptorchidism whose symptoms resemble the well-known 9p deletion syndrome or 9p monosomy. We also noted congenital hydrocephalus, oculocutaneous albinism, retinal coloboma, and megalocornea, which are not typical features of 9p monosomy. When a new albinism gene was localized to 9p (Chintamaneni et al., Biochem Biophys Res Commun 1991;178:227-235; Murty et al., Genomics 1992;13:227-229), we hypothesized that our patient had the 9p deletion syndrome plus albinism, with the deletion involving the albinism gene. We used FISH probes to test this hypothesis and found that the 9p region was normal, therefore excluding the 9p deletion syndrome. To our knowledge, the association of congenital hydrocephalus, albinism, megalocornea, and retinal coloboma has not been described in the literature. The purpose of this report is to describe this new association of congenital ocular and cerebral anomalies in a syndromic child.
Asunto(s)
Anomalías Múltiples/genética , Albinismo Oculocutáneo/genética , Cromosomas Humanos Par 9/genética , Coloboma/genética , Córnea/anomalías , Hidrocefalia/genética , Retina/anomalías , Anomalías Múltiples/patología , Adulto , Albinismo Oculocutáneo/patología , Coloboma/patología , Criptorquidismo/genética , Análisis Mutacional de ADN , Humanos , Hidrocefalia/patología , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , SíndromeRESUMEN
We report on prenatal diagnosis by FISH of a sporadic 22q11 deletion associated with DiGeorge syndrome (DGS) in two fetuses after an obstetric ultrasonographic examination detected cardiac anomalies, an interrupted aortic arch in case 1 and tetralogy of Fallot in case 2. The parents decided to terminate the pregnancies. At necropsy, fetal examination showed characteristic facial dysmorphism associated with congenital malformations, confirming full DGS in both fetuses. In addition to the 22q11 deletion, trisomy X was found in the second fetus and a reciprocal balanced translocation t(11;22) (q23;q11) was found in the clinically normal father of case 1. These findings highlight the importance of performing traditional cytogenetic analysis and FISH in pregnancies with a high risk of having a deletion.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 22/fisiología , Síndrome de DiGeorge/diagnóstico , Enfermedades Fetales/diagnóstico , Diagnóstico Prenatal , Aborto Inducido , Adulto , Cósmidos , Sondas de ADN , Síndrome de DiGeorge/genética , Femenino , Enfermedades Fetales/genética , Cardiopatías Congénitas , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Embarazo , Translocación Genética , TrisomíaRESUMEN
DiGeorge syndrome, and more widely the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. A critical region of 500 kb has been delimited within which maps the breakpoint of a balanced translocation associated with mild CATCH 22 phenotypes. We report the isolation from this critical region of a novel gene, DGCR6, which maps 115 kb centromeric to the balanced translocation breakpoint. The DGCR6 gene product shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ-line cells development, and with the human laminin. gamma-1 chain, which upon polymerization with alpha- and beta- chains forms the laminin molecule. Laminin binds to cells through interaction with a receptor and has functions in cell attachment, migration and tissue organization during development. DGCR6 could be a candidate for involvement in the DiGeorge syndrome pathology by playing a role in neural crest cell migration into the third and fourth pharyngeal pouches, the structures from which derive the organs affected in DiGeorge syndrome.
Asunto(s)
Síndrome de DiGeorge/genética , Drosophila melanogaster/genética , Laminina/genética , Proteínas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Southern Blotting , Mapeo Cromosómico , Secuencia Conservada , Cósmidos , Bases de Datos Factuales , Proteínas de la Matriz Extracelular , Humanos , Datos de Secuencia Molecular , Proteínas Nucleares , Polimorfismo Genético , Eliminación de Secuencia , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
Molecular studies have shown microdeletions in region q11 of chromosome 22 in nearly all patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes (DGS, VCFS and CTAFS, respectively) and in a high percentage of non-syndromic familial cases of conotruncal defects (CTD). CTD account for roughly a fourth to a third of all non-syndromic congenital heart defects (CHD), thus, 22q11 could harbor a major genetic factor of CHD. We searched for a 22q11 microdeletion in familial cases of non-syndromic CTD. Thirty-six cases of various isolated CTD, that is without history of hypocalcemia, immune deficiency, absent thymus, and dysmorphic appearance, were selected. With 48F8, a cosmid probe localized in the smallest deleted region of the DiGeorge critical region (DGCR), we found no deletions by fluorescence in situ hybridization in these 36 affected individuals of 16 families with recurrent CTD. Moreover, D22S264, a microsatellite localized at the distal part of the largest deleted region, was used to genotype the patients. Thirty-two patients out of 37 were heterozygous and hence not deleted at this locus, whereas 5 were uninformative. In conclusion, there are no large deletions in familial cases of various CTD, whether these defects are identical or not within a family. This result does not rule out other minor anomalies in this chromosomal region.
Asunto(s)
Cromosomas Humanos Par 22 , Cardiopatías Congénitas/genética , Adolescente , Adulto , Niño , Preescolar , Deleción Cromosómica , Síndrome de DiGeorge/genética , Repeticiones de Dinucleótido , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Linaje , RecurrenciaRESUMEN
The human gene HIRA lies within the smallest critical region for the DiGeorge syndrome (DGS), a haploinsufficiency developmental disorder associated with instertitial deletions in most patients in a juxtacentromeric region of chromosome 22. The HIRA protein sequence can be aligned over its entire length with Hir1 and Hir2, two yeast proteins with a regulatory function in chromatin assembly. The HIRA transcription unit was found to spread over approximately 100 kb of the DGS critical region. The human transcript is encoded from 25 exons between 59 and 861 bp in size. Domains of highest conservation with Hir1 and Hir2 are encoded from exons 1-11 and 13-25, respectively. The amino- and carboxy-terminal regions of homology are separated from each other by a domain unique to HIRA that is encoded from a single exon. Seven WD repeats are conserved between yeast and man in the amino-terminal region of the HIR proteins. Individual repeats were found to be encoded from one, two, or three exons of the HIRA gene. End sequences have been obtained for all 24 introns, opening the way to PCR amplification of the entire coding sequence starting from genomic DNA. Point mutations can also be sought in 16 of the 24 introns that are readily PCR-amplifiable.
Asunto(s)
Proteínas de Ciclo Celular , Cromosomas Humanos Par 22 , Síndrome de DiGeorge/genética , Proteínas Nucleares/genética , Secuencias Repetitivas de Ácidos Nucleicos , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción/genética , Secuencia de Aminoácidos , Composición de Base , Secuencia de Bases , Mapeo Cromosómico , ADN Complementario , Exones , Chaperonas de Histonas , Humanos , Datos de Secuencia Molecular , Proteínas Represoras/genéticaRESUMEN
We have determined the parental origin of the deleted chromosome 22 in 29 cases of DiGeorge syndrome (DGS) using a CA-repeat mapping within the commonly deleted region, and in one other case by using a chromosome 22 short arm heteromorphism. The CA-repeat was informative in 21 out of 29 families studied and the deleted chromosome was of maternal origin in 16 cases (72%). When these data are pooled with recent results from the literature, 24 de novo DGS, velo-cardio-facial syndrome (VCFS) and isolated conotruncal cardiac disease deletions are found to be of maternal origin and 8 of paternal origin, yielding a chi 2 of 8 with a probability level lower than 0.01. These data, and review of the literature on familial DGS/VCFS and isolated conotruncal cardiopathies suggest that there is a strong tendency for the 22q11.2 deletions to be of maternal origin.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 22/genética , Síndrome de DiGeorge/genética , Cara/anomalías , Cardiopatías Congénitas/genética , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
We report the physical mapping of 30 microsatellite markers specific for chromosome 22 by PCR amplification of DNA from hybrids that divide the long arm into 27 subregions. This work permits further refining of the genetic linkage ordering previously published.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 22 , Secuencias Repetitivas de Ácidos Nucleicos , Secuencia de Bases , ADN Satélite/química , Marcadores Genéticos , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Deletions of the 22q11.2 have been associated with a wide range of developmental defects (notably DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome and isolated conotruncal cardiac defects) classified under the acronym CATCH 22. A DiGeorge syndrome patient bearing a balanced translocation whose breakpoint maps within the critical region has been previously described. We report the construction of a cosmid contig spanning the translocation breakpoint and the isolation of a gene mapping 10 kb telomeric to the breakpoint. This gene encodes a novel putative adhesion receptor protein, which could play a role in neural crest cells migration, a process which has been proposed to be altered in DiGeorge syndrome.
Asunto(s)
Adhesión Celular , Síndrome de DiGeorge/genética , Proteínas de la Membrana/genética , Translocación Genética , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 22 , Clonación Molecular , ADN Complementario , Humanos , Glicoproteínas de Membrana , Datos de Secuencia Molecular , Complejo GPIb-IX de Glicoproteína Plaquetaria , Homología de Secuencia de AminoácidoRESUMEN
DiGeorge syndrome (DGS) is a developmental defect which associates hypo- or aplasia of the thymus and parathyroids, facial dysmorphism and conotruncal cardiac malformations. The etiological factor in a great majority of DGS patients is monosomy for the 22q11.2 chromosomal region either through a large interstitial deletion of that region (inherited or de novo) or through an unbalanced translocation involving chromosome 22. In one instance, a balanced translocation of chromosome 22 was associated with a DGS phenotype. Extensive analyses of this region of chromosome 22 has led to the obtention of precise physical maps of the corresponding genomic region, to the cloning of the balanced translocation breakpoint and to the isolation of different genes from the minimal critical deleted region.
Asunto(s)
Anomalías Múltiples/clasificación , Aberraciones Cromosómicas/genética , Deleción Cromosómica , Cromosomas Humanos Par 22/ultraestructura , Síndrome de DiGeorge/genética , Anomalías Inducidas por Medicamentos/genética , Anomalías Múltiples/etiología , Anomalías Múltiples/genética , Animales , Aberraciones Cromosómicas/etiología , Aberraciones Cromosómicas/patología , Trastornos de los Cromosomas , Mapeo Cromosómico , Síndrome de DiGeorge/etiología , Femenino , Genes , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones del Embarazo , Ratas , Síndrome , Translocación Genética , Tretinoina/efectos adversosRESUMEN
The authors have studied a series of 23 DiGeorge syndrome patients by prometaphase chromosome analysis and/or by FISH with a set of 6 cosmid probes spanning the previously described commonly deleted region. Four patients display a cytogenetically visible interstitial deletion in band 22q11.2, whereas the other 18 patients exhibit a molecular deletion evidenced only by FISH analysis. For 21 of the patients studied, the deletion encompasses the 6 loci tested, while for one, only the most telomeric of these loci is conserved. The last patient does not show any deletion with the probes used.
Asunto(s)
Aberraciones Cromosómicas , Síndrome de DiGeorge/genética , Hibridación Fluorescente in Situ , Eliminación de Secuencia , Adolescente , Niño , Preescolar , Síndrome de DiGeorge/sangre , Síndrome de DiGeorge/inmunología , Síndrome de DiGeorge/patología , Cara/anomalías , Femenino , Marcadores Genéticos , Cardiopatías Congénitas/genética , Humanos , Hipocalcemia/genética , Lactante , Masculino , Sondas de Oligonucleótidos , Glándulas Paratiroides/patología , Fenotipo , Subgrupos de Linfocitos T , Timo/patologíaRESUMEN
We describe the relative ordering, by fluorescence in situ hybridization, of cosmid loci and translocation breakpoints in the DiGeorge syndrome (DGS) critical region of chromosome 22. This physical map enables us to define a large region, commonly deleted in a majority of affected patients, and the smallest deleted region which, when lost, is sufficient to produce DGS. In four instances, a similar large deleted region is observed in a familial context. In these pedigrees, the deletion is encountered in one parent with mild features of the disease.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 22 , Síndrome de DiGeorge/genética , Adulto , Línea Celular , Niño , Deleción Cromosómica , Cósmidos , Síndrome de DiGeorge/patología , Femenino , Humanos , Células Híbridas , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Masculino , Sondas Moleculares , Linaje , Fenotipo , Embarazo , Translocación GenéticaRESUMEN
DiGeorge syndrome is a human developmental disorder resulting in hypoplasia of the thymus and parathyroids, and conotruncal heart defects. We recently isolated four genes with zinc finger DNA binding motifs mapping to chromosome 22q11.2 DiGeorge critical region. We now report that one of them, ZNF74 gene, is hemizygously deleted in 23 out of 24 DiGeorge syndrome patients tested. ZNF74 mRNA transcripts are detected in human and mouse embryos but not in adult tissues. Sequence analysis of a corresponding cDNA reveals an an open reading frame encoding 12 zinc finger motifs of the Kruppel/TFIIIA type as well as N-terminal and C-terminal non-zinc finger domains. These results suggest that changes in the dosage of a putative transcription factor through ZNF74 hemizygous deletion may be critical for DiGeorge developmental anomalies.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 22/ultraestructura , Síndrome de DiGeorge/genética , Eliminación de Gen , Genes , Dedos de Zinc/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Preescolar , Mapeo Cromosómico , ADN Complementario/genética , Femenino , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , FenotipoRESUMEN
Fifty-nine NotI linking clones have been isolated from a flow-sorted chromosome 22 cosmid library and mapped using fluorescence in situ hybridization and/or a panel of somatic cell hybrids. Fourteen clones map to the short arm of chromosome 22, 31 to the long arm, and 9 to other chromosomes; 5 clones could not be unambiguously mapped. To identify potentially informative genetic markers, the chromosome 22 clones were screened for poly(CA) sequences; 24 positively hybridizing clones, 10 on the long arm and 14 on the short arm, were identified. These clones will be useful for constructing a long-range restriction map of chromosome 22 and may facilitate the cloning of chromosome 22 genes.
Asunto(s)
Cromosomas Humanos Par 22 , Desoxirribonucleasas de Localización Especificada Tipo II , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Cósmidos , ADN/genética , Biblioteca de Genes , Humanos , Células Híbridas , Oligodesoxirribonucleótidos/genética , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease predisposing carriers to develop nervous system tumours. To identify the genetic defect, the region between two flanking polymorphic markers on chromosome 22 was cloned and several genes identified. One is the site of germ-line mutations in NF2 patients and of somatic mutations in NF2-related tumours. Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans.
Asunto(s)
Genes de la Neurofibromatosis 2 , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Deleción Cromosómica , Cromosomas Humanos Par 22 , Clonación Molecular , ADN de Neoplasias , Células Germinativas , Células HeLa , Humanos , Células Híbridas , Ratones , Datos de Secuencia Molecular , Mutación , Neurofibromina 2 , Mutación Puntual , Mapeo Restrictivo , Homología de Secuencia de Aminoácido , Células Tumorales CultivadasRESUMEN
The B x H recombinant inbred strains of mice were used to undertake a genetic analysis of the maternal factors controlling the survival of trisomy 16 fetuses. The data presented indicate that the prevalence of trisomic fetuses on day 15 of gestation varies significantly with the genetic background of the mother. The strain difference in the frequency of trisomy appears to be the result of selective elimination of trisomic fetuses. Various statistical methods employed to elucidate the genetic architecture of the trait from the recombinant inbred strains data indicate that the number of loci involved in the selection process ranges from one to five. Linkage association with two loci has been found; however, with a low probability level (P = 0.292).
Asunto(s)
Aberraciones Cromosómicas/embriología , Ratones/genética , Trisomía , Animales , Blastocisto , Trastornos de los Cromosomas , Cruzamientos Genéticos , Muerte Fetal/genética , Reabsorción del Feto/genética , Ratones/embriología , Ratones Endogámicos C3H/genética , Ratones Endogámicos C57BL/genética , Translocación GenéticaRESUMEN
A better method was developed for analysis and identification of protein and DNA components of gel-shift assays. The protein-DNA complexes, separated in polyacrylamide gels, were transferred onto stacked nitrocellulose and anion-exchange membranes. The proteins, bound to nitrocellulose, were identified by immunoblotting, while the DNA, which bound only to the anion-exchange membrane, was detected by autoradiography. The technique readily identified thyroid hormone receptors interacting with response elements representing inverted or direct repeats of the consensus half-site AGGTCA. In addition, specific antisera identified both the thyroid hormone and the retinoic acid receptors in heterodimeric complexes. Adding a third membrane and digoxigenin-labeled DNA probes allowed separate detection of [125I]T3 (labeled 3,5,3'-L-triiodothyronine), DNA, and protein from a single gel-shift reaction. The usefulness of this technique was also demonstrated by detecting the transcription factors P75gag-v-erbA and Jun in shifted complexes. Finally, proteins and DNA transferred to anion-exchange membranes can be eluted and subjected to further study. The combination of the gel shift and the immunoblot approaches (called "Shift-Western blotting") allows identification of the individual components of protein-DNA complexes containing multiple transcription factors, their cognate DNA elements and, when applicable, also the ligand.