RESUMEN

Intrachromosomal insertions are complex structural rearrangements that are challenging to interpret using classical cytogenetic methods. We report a male patient carrying a recombinant X chromosome derived from a maternally inherited intrachromosomal insertion. The patient exhibited developmental delay, intellectual disability, behavioral disorder, and dysmorphic facial features. To accurately identify the rearrangements in the abnormal X chromosome, additional cytogenetic studies were conducted, including fluorescence in situ hybridization (FISH), multicolor-banding FISH, and array comparative genomic hybridization. The results showed a recombinant X chromosome, resulting in a 13.05 Mb interstitial duplication of segment Xp22.33-Xp22.13, which was inserted at cytoband Xq26.1. The duplicated region encompasses 99 genes, some of which are associated with the patient's clinical manifestations. We propose that the combined effects of the Xp-duplicated genes may contribute to the patient's phenotype.

Asunto(s)

Aberraciones Cromosómicas , Discapacidad Intelectual , Humanos , Masculino , Hibridación Fluorescente in Situ , Hibridación Genómica Comparativa , Análisis Citogenético , Discapacidad Intelectual/genética , Cromosomas Humanos X/genética , Duplicación Cromosómica

RESUMEN

Deletion of the long arm of chromosome 18 is one of the most common segmental aneusomies compatible with life and usually involves a deletion of the terminal chromosomal region. However, the mechanisms implicated in the stabilization of terminal deletions are not well understood. In this study, we analyzed a girl with moderate mental retardation who had a cytogenetically visible terminal 18q deletion. In order to characterize the breakpoint in the terminal 18q region, we used fluorescence In situ hybridization (FISH) with bacterial artificial chromosomes (BACs) and pan-telomeric probes and also the array technique based on comparative genomic hybridization (array-CGH). FISH with pan-telomeric probes revealed no signal in the terminal region of the deleted chromosome, indicating the absence of normal telomere repeat (TTAGGG)n sequences in 18q. We suggest that neo-telomere formation by chromosome healing was involved in the repair and stabilization of this terminal deletion.

Asunto(s)

Deleción Cromosómica , Cromosomas Humanos Par 18 , Hibridación Genómica Comparativa/métodos , Hibridación Fluorescente in Situ/métodos , Telómero/genética , Adolescente , Femenino , Humanos , Discapacidad Intelectual/genética , Cariotipificación , Secuencias Repetitivas de Ácidos Nucleicos/genética , Telómero/metabolismo

RESUMEN

Supernumerary marker chromosomes (sSMC) may or may not be associated with an abnormal phenotype, depending on the presence of euchromatin, on their chromosomal origin and whether they are inherited. Over 80% of sSMCs are derived from acrocentric chromosomes and half of them include the short arm of chromosome 15. Generally, they appear as bisatellited isodicentric marker chromosomes, most of them are symmetric. These chromosomes are normally originated de novo and are associated with mild to severe intellectual disability but not with physical abnormalities. We report on a patient with an SMC studied using classical and molecular cytogenetic procedures (G and C banding, NOR staining, painting and centromeric fluorescent in situ hybridization (FISH), BAC-FISH, and SKY). The MLPA technique and DNA polymorphic markers were used in order to identify its parental origin. The marker chromosome, monosatellited and monocentric, was found to be derived from a maternal chromosome 15 and was defined as 15pter-q21.2. This is the report of the largest de novo monosatellited 15q marker chromosome ever published presenting detailed cytogenetic and clinical data. It was associated with a phenotype including cardiac defect, absence of septum pellucidum, and dysplasia of the corpus callosum.

Asunto(s)

Anomalías Múltiples/genética , Cromosomas Humanos Par 15/genética , Marcadores Genéticos , Trisomía , Síndrome Acrocallosal/genética , Discapacidades del Desarrollo/genética , Femenino , Cardiopatías Congénitas/genética , Humanos , Lactante , Fenotipo , Tabique Pelúcido/anomalías , Cariotipificación Espectral

RESUMEN

BACKGROUND: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma. METHODS: In this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data. RESULTS: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. In particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis. CONCLUSION: In this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker.

Asunto(s)

Neoplasias Óseas/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Osteonectina/biosíntesis , Osteopontina/biosíntesis , Osteosarcoma/metabolismo , Trombospondinas/biosíntesis , Adolescente , Adulto , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/fisiología , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Remodelación Ósea/genética , Proliferación Celular , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteonectina/genética , Osteonectina/fisiología , Osteopontina/genética , Osteopontina/fisiología , Osteosarcoma/genética , Osteosarcoma/patología , Estudios Prospectivos , Trombospondinas/genética , Trombospondinas/fisiología

RESUMEN

Tumors of the central nervous system are the second most frequent malignancy of childhood, accounting for the majority of cancer-related deaths in this age group. Among these tumors, medulloblastomas (MB) remain in need of further genomic characterization toward understanding of pathogenesis and outcome predictors. Eight pediatric embryonal brain tumors were analyzed: five MB (one being desmoplastic), one PNET, one medulloepithelioma, and one ependymoblastoma. Analyses identified genomic imbalances, including the gain of 16p and the nonsyntenic coamplification of MYCN and TERT loci. More detailed FISH analysis showed that coamplification of MYCN and TERT in one of the MBs manifested as dispersed nuclear speckling, consistent with the presence of double minute chromosomes. There was considerable cell-to-cell copy number heterogeneity present, but it was clear that both genes were amplified concordantly. The amplification of oncogenes seems to play an important role in the pathogenesis of MB, and the association between MYCN and TERT amplifications and poor prognosis has not been well recognized. The uncharacteristic pattern of genomic imbalances detected in MB tumors may be a reflection of the characteristics of these tumors occurring in South America.

Asunto(s)

Neoplasias Cerebelosas/genética , Amplificación de Genes , Meduloblastoma/genética , Metafase , Adolescente , Niño , Preescolar , Proteínas de Unión al ADN/genética , Femenino , Genes myc , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , América del Sur , Telomerasa/genética

RESUMEN

We report on a patient with hydrocephaly, penoscrotal transposition, oligodactyly, and minor anomalies. Comprehensive cytogenetic studies involving both classical cytogenetic methods and mBAND analysis were used to show a stable dicentric rearranged chromosome 13 that result in a 46,XY,psu dic(13;13)(13pter --> 13q32::13q11 --> 13pter) de novo karyotype. This aberration probably arose as a consequence of unequal sister chromatid breakage repair events. This report is the first to describe all of the most severe features associated with partial monosomy in one patient. Moreover, the delineation of monosomy 13q32 --> qter in this patient facilitates identification of the developmental genes responsible for the clinical features within this region of chromosome 13.

Asunto(s)

Anomalías Múltiples/patología , Cromosomas Humanos Par 13 , Análisis Citogenético , Eliminación de Gen , Hidrocefalia/patología , Anomalías Urogenitales/patología , Anomalías Múltiples/genética , Rotura Cromosómica , Dedos/anomalías , Duplicación de Gen , Humanos , Hidrocefalia/genética , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , Monosomía , Región Organizadora del Nucléolo/metabolismo , Tinción con Nitrato de Plata , Dedos del Pie/anomalías , Tomografía Computarizada por Rayos X , Anomalías Urogenitales/genética

RESUMEN

OBJECT: The purpose of this study was to examine chromosomal gains and losses in 11 pediatric adamantinomatous craniopharyngiomas by using comparative genomic hybridization (CGH), as well as to review the cytogenetic literature that has contributed to the characterization of these tumors. One source of confusion in the cytogenetic and CGH literature concerning craniopharyngioma is that the authors of most studies fail to distinguish between pediatric and later-onset forms of the disease. Thus, this study was focused on pediatric craniopharyngioma. METHODS: To determine an overview of the genetic events leading to the development of these tumors, 10 adamantinomatous craniopharyngiomas were analyzed using CGH; none of the tumor specimens demonstrated gains or losses of DNA sequence. CONCLUSIONS: In view of these findings as well as those published in the majority of previous cytogenetic studies of craniopharyngiomas, the authors conclude that the recurrent acquisition of chromosomal imbalances does not play a major role in tumorigenesis and that chromosomal gains and losses are a relatively rare event in primary tumors of pediatric origin.

Asunto(s)

Aberraciones Cromosómicas , Craneofaringioma/genética , ADN de Neoplasias/análisis , Neoplasias Hipofisarias/genética , Adolescente , Edad de Inicio , Transformación Celular Neoplásica/genética , Niño , Preescolar , Inestabilidad Cromosómica , Citogenética , Femenino , Humanos , Masculino , Hibridación de Ácido Nucleico , Recurrencia

RESUMEN

We report two pediatric patients with unclassified myelodysplastic syndrome (MDS) by the French-American-British (FAB) group. Both cases had clinical and hematological peculiarities, which had not been described yet. The cytogenetic alterations were 4q deletion and the Philadelphia (Ph) chromosome which appeared at different moments of the disease. One patient showed the Ph chromosome at disease transformation and the other at diagnosis. The different breakpoints at 4q and the presence of Ph could be a marker of this form of MDS. The association of clinical and hematological findings suggests the possibility of a new group of pediatric MDS.

Asunto(s)

Cromosomas Humanos Par 4 , Síndromes Mielodisplásicos/genética , Cromosoma Filadelfia , Preescolar , Deleción Cromosómica , Análisis Citogenético , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Síndromes Mielodisplásicos/clasificación