Sira Moreno

Chromosomal composition of a series of 22 human low-grade gliomas

G-banded chromosomal analysis was performed on direct and/or in vitro cultures of 22 low-grade gliomas, including nine grade I-II astrocytomas, nine oligodendrogliomas, one mixed tumor oligodendroglioma-astrocytoma, and three ependymomas. Normal diploid stem lines were present in most astrocytomas and oligodendrogliomas, whereas, all three ependymomas displayed polyploid modal numbers. However, secondary cell lines showed the presence of clonal recurrent numerical abnormalities, mainly polysomy 7, monosomy 10 and 22, and loss of the Y chromosome. Clonal structural rearrangements were present with a low incidence; they mainly involved chromosomes #1 and #7. These patterns of chromosome involvement seem to correlate with the scarce previous cytogenetic banding data available from low-grade gliomas. They are also similar to the chromosome alterations found in high-grade gliomas.

Chromosomal involvement secondary to −22 in human meningiomas☆

Cytogenetic analyses have been performed on cultures in vitro from 32 human meningiomas, seeking chromosomal anomalies in addition to characteristic monosomy 22. Eight cases showed stem lines with normal karyotype, whereas, monosomy 22 as the only chromosomal deviation characterized the stem line of ten tumors. In 14 samples stem lines or modal numbers displaying numerical deviations (other than -22) and/or structural rearrangements were found. A hyperdiploid modal number was present in three, whereas, it was hypodiploid in the remainder. Numerical deviations in these tumors involved mainly #14 by losses, and also #22; recurrent structural rearrangements involving 1p and 11p were also characteristic features. Thus, these results could imply that involvement of #14, 1p, and 11p would be a form of clonal evolution secondary to monosomy 22 in certain meningiomas.

Deletion 3p in two lung adenocarcinomas metastatic to the brain

Cytogenetic analysis by direct and in vitro preparation of brain metastatic lesions from two lung adenocarcinomas have shown the presence of a recurrent chromosomal abnormality, del(3p). These results add new evidence about the presence of 3p- marker chromosomes in adenocarcinoma of the lung.

Cytogenetic analysis in human neurinomas

In a recent report, Seizinger et al. [1], using a molecular genetic approach, have shown that acoustic neuroma is associated with loss of genes on chromosome #22, suggesting a mechanism of tumorigenesis similar to that found in embryonal tumors [2-6]. According to their findings, loss of constitutional heterozygosity of loci of #22 was evident in 44% of the informative cases (with the used probes), including both patients with unilateral and bilateral acoustic neuromas. As a part of a study on cytogenetic features of tumors of the nervous system, we have performed chromosome studies on seven samples from neuromas (three acoustic and four spinal tumors). Cellular dissaggregation of the tumor samples was performed as described previously [7, 8], and all cases were studied in fixations from primary cultures after 8-19 days of growth in vitro. At least 50 G-banded metaphases were analyzed in each tumor. In all seven cases a normal diploid stem line karyotype was found; however, five displayed karyologic abnormalities in side lines. Monosomy #22 was evident in three tumors, one of them also showing loss of #17. Y chromosome loss characterized the secondary line in the fourth, whereas, monosomy 18 with a 13q ÷ marker chromosome was evident in the fifth. In 1972, Mark [9] found normal karyotypes in in vitro fixations from three neurinomas, whereas, four others had pseudodiploid-hy podiploid stem lines. The chromosomal deviations mainly involved chromosomes of groups B, C, E [17, 18] and G, including numerical and structural abnormalities. These cytogenetic findings seem to be in accordance with the molecular data now available, suggesting monosomy 22 in some cells of acoustic neurinomas. The presence of normal diploid stem lines in our cases would be a contradictory result; however, Seizinger et al. [1] also found hybridization signals with the tumor DNAs, other than those corresponding to alleles revealed by the specific probes. These authors stated that nontumor cells might contaminate the samples or, alternatively, the tumors could be composed of a mosaic of cells, some of them showing normal karyotypes. This fact would be in accordance with the histopathologic data suggesting that neurinomas include several cell types [10]. In addition, the in vitro morphology of the cultured cells in our cases was compatible with neurinoma origin. Finally, microdeletions on #22, not detectable at the cytogenetic level, could be also present in apparently normal diploid cases. Further research combining both molecular and high resolution chromosomal analysis on the same samples will add interesting data on the possible specific involvement of #22 chromosome in tumorigenesis of human neurinomas, including acoustic tumors.

Involvement of 9p in metastatic ovarian adenocarcinomas

By a direct method and after in vitro culture, we cytogenetically analyzed five ovarian adenocarcinomas, using six samples of ascitic fluid. The structural aberrations included rearrangements of chromosomes 1 and 3, in agreement with the results of other researchers. The long arm of chromosome 6 was rearranged in three samples, but no translocation t(6;14) was found. Rearrangements involving 9p were present in all cases, with breakpoints at p13 or p22-23.

Cytogenetic follow-up from direct preparation to advanced in vitro passages of a human malignant glioma☆☆☆

In order to evaluate which cytogenetic evolutionary patterns take place during the in vitro establishment of a permanent glioma cell line, cytogenetic follow-up was performed on direct preparations and primary cultures from a malignant astrocytoma and on serial passages for more than 2 years of in vitro propagation. Sixteen passages were studied, and the presence of a marker chromosome in direct preparations and after in vitro growth permitted us to identify the clonal evolution of the resulting permanent cell line. Near-triploid cells present in the direct study became the main cell population in vitro; chromosomal losses and the acquisition of a few new marker chromosomes were also characteristic features, leading to a stable modal number of around 60 chromosomes in the last passages analyzed. The results provide new evidence of the existence of more than one pattern of chromosomal evolution during the in vitro establishment of human gliomas.