Joyce Anderson Duffles Andrade

Comparative genomic hybridization analysis identifies gains of 1p35 p36 and chromosome 19 in osteosarcoma

Osteosarcomas (OS) are aggressive tumors of the bone and often have a poor prognosis. Conventional cytogenetic analyses of OS have revealed highly complex karyotypes, with numerous abnormalities. In this study, we analyzed 18 untreated OS tumors from 17 patients of the younger incidence age group by comparative genomic hybridization (CGH), 4 tumors by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Comparative genomic hybridization identified frequent copy number changes of the chromosomal region 1p (10/17) and gain of part or all of chromosome 19(8/17). In addition gains were observed at 5p(3/17), 8q(3/17), 16p(3/17), and 17p(5/17); and losses at chromosomes 2q(3/17), 10(4/17) and 13(3/17). High level gains were detected in the 8q23 approximately q24 region in two tumors as well as at 17p in one primary and a metastatic tumor. Minimal regions of gain were present at 1p35 approximately p36.3 (8/17); 5p14 approximately p15.2 (3/17), and 8q22 approximately q24.3 (3/17). SKY analysis demonstrated that OS has a complex pattern of clonal and non-clonal rearrangements and helped confirm the structural basis for the imbalances detected by CGH. Spectral karyotyping confirmed an overall pattern of chromosomal gain affecting 1p in all four tumors. Fluorescence in situ hybridization analysis from these tumors confirmed the gain of the 1p36 region in 2 tumors as determined by CGH analysis as well as the amplification of 8q.

Y‐chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y‐mosaicism

The frequency of gonadoblastoma is high in patients with Turners syndrome bearing cells with Y or partial Y‐chromosome. About 60% of patients with Turners syndrome have a 45,X karyotype. In 30% of them a Y‐sequence is disclosed by DNA analysis. To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ3 specific primers was carried out to detect different Y‐sequences in the DNA of peripheral lymphocytes from patients with Turners syndrome.

TRAP-silver staining, a highly sensitive assay for measuring telomerase activity in tumor tissue and cell lines

Measurement of telomerase activity in clinically obtained tumor samples may provide important information for use as both a diagnostic marker and a prognostic indicator for patient outcome. In order to evaluate telomerase activity in tumor tissue without radiolabeling the product, we developed a simple telomeric repeat amplification protocol-silver-staining assay that is less time-consuming, is safe and requires minimal equipment. In addition, we determined the sensitivity of the silver-staining method by using extracts of telomerase-positive thyroid carcinoma cell lines which were serially diluted from 5,000 to 10 cells. Telomerase activity was also assayed in 19 thyroid tumors, 2 normal controls and 27 bone marrow aspirates. The results indicate that the technique permits the detection of telomerase activity from 5000 to as few as 10 cells. We propose that it could be immediately applicable in many laboratories due to the minimal amount of equipment required.

MYCN Gene Amplification: Identification of Cell Populations Containing Double Minutes and Homogeneously Staining Regions in Neuroblastoma Tumors

Neuroblastoma is the second most common solid tumor occurring in children. Amplification of the MYCN oncogene is associated with poor prognosis. To identify neuroblastoma tumors with MYCN amplification, we studied the number of copies of MYCN in interphase cells by fluorescence in situ hybridization in 20 neuroblastoma patients. MYCN amplification appeared in 7 tumor specimens. Interphase and metaphase studies showed a tumor cell population with both forms of amplification, double minutes and homogeneously staining regions, in two patients. These patients showed a smaller tumor cell subpopulation with the presence of more than one homogeneously staining region, suggesting that gene amplification was undergoing karyotype evolution.

Bilateral retinoblastoma associated with 13q− mosaicism: Possible manifestation of a germinal mutation

Fifteen retinoblastoma patients were studied cytogenetically using G- and R-banding techniques. One patient showed 13q-mosaicism. It is suggested that a postzygotic deficiency in mosaic cases and in tumoral cells may be secondary to germinal mutation.

Myelodysplastic syndrome in childhood: report of two cases with deletion of chromosome 4 and the Philadelphia chromosome

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.

Duplication 4p and deletion 4p (Wolf-Hirschhorn syndrome) due to complementary gametes from a 3:1 segregation of a maternal balanced t(4;13)(p16;q11) translocation.

We present clinical and cytogenetic data on a family with a t(4;13)(p16;q11) translocation present in four generations. The balanced translocation resulted in one individual with monosomy 4p and one individual with trisomy 4p, due to 3:1 segregation. The male patient with trisomy 4p was fertile and transmitted the extra chromosome to his daughter.

Retinoblastoma: análise cromossômica

O artigo refere o resultado da analise cromossomica de 27 portadores de retinoblastoma uni ou bilateral, de ambos os sexos, esporadicos ou familiais, virgens de tratamento ou apos 6 meses do termino de quimioterapia sistemica, triados no Ambulatorio de Oftalmologia do Hospital A.C. Camargo da Fundacao Antonio Prudente/SP. Foi dada preferencia aqueles que apresentavam, no quadro clinico geral, malformacoes congenitas, alteracoes fenotipicas ou retardo mental. Encontrou-se cromossomopatia inespecifica em 2 pacientes submetidos a poliquimioterapia e cromosssomopatia conhecidas em outros 3 (47,XX+G; 46,XY/47,XY+G; 46,XY/46, XY13q-). Os autores discutem os resultados, a associacao de cromossomopatia e retinoblastoma e a indicacao do exame do cariotipo nesses pacientes

Sister chromatid exchange frequency in a retinoblastoma mosaic patient with del(13)

The frequencies of sister chromatid exchange (SCE) were investigated in different cell populations derived from a patient with retinoblastoma and 46,XY/46,XY,del(13) (q12.3q21.2) mosaicism. No differences in spontaneous or mitomycin C-induced SCE were detected between cell populations.