Cytogenetic studies in twenty human brain tumors: Association of no. 22 chromosome abnormalities with tumors of the brain

123

Astrocytomas, including glioblastoma multiforme, represent the most frequent and deadly primary neoplasms of the human nervous system. Despite a number of previous cytogenetic and oncogene studies primarily focusing on malignant astrocytomas, the primary mechanism of tumor initiation has remained obscure. The loss or inactivation of "tumor suppressor" genes are thought to play a fundamental role in the development of many human cancers. Thus, we have analyzed astrocytomas of various histological malignancy grades with polymorphic DNA markers to search for specific chromosomal deletions potentially pointing to loci containing tumor suppressor genes. Loss of constitutional heterozygosity indicating chromosomal loss or deletions was most frequently seen for markers on the short arm of chromosome 17 in 50% of the informative tumors (5 of 10 informative cases) and, to a lesser extent, for markers on chromosomes 1 and 10. Deletions on chromosome 17p were seen in both low-grade and high-

Section: Discussionmentioning

confidence: 99%

“…15 and 16). Chromosomes 1, 7, and 10 were selected because of previous reports on their frequent numerical and structural aberrations in glial tumors (17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas.

El-Azouzi

Chung

Farmer

et al. 1989

123

“…Loss or deletions of chromosome 22 (22qll-qter) have been associated with meningiomas and gliomas (31,32), and a recent study demonstrated that sequences on chromosome 22 are nonrandomly lost in acoustic neuromas (33). Reciprocal translocations involving chromosomes 11 and 22 have been observed in neuroepitheliomas (34) and in a neuroendocrine tumor of the small intestine (35).…”

mentioning

confidence: 99%

Cloning of a cDNA encoding the rat high molecular weight neurofilament peptide (NF-H): developmental and tissue expression in the rat, and mapping of its human homologue to chromosomes 1 and 22.

Lieberburg

Spinner

Snyder

et al. 1989

“…The propensity of low-malignancy-grade astrocytomas to relapse with recurrent tumor that often display a malignant progression (4,5) accentuates the severity of the disease. Several cytogenetic analyses of high-malignancy-grade tumors have described frequent chromosome aberrations in direct preparations and short-term cultures of astrocytomas (6)(7)(8)(9)(10)(11). In contrast, studies involving analysis of astrocytic tumors of low malignancy grade have consistently demonstrated cells with normal karyotypes (12,13).…”

mentioning

confidence: 99%

Mitotic recombination of chromosome 17 in astrocytomas.

James¹,

Carlbom²,

Nordenskjöld³

et al. 1989

250

Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. (16), and here we have applied such analysis to a series of gliomas to examine clonal genotypic changes in these tumors. Our data indicate that loss of sequences on chromosome 17p, an aberration that has not been cytogenetically associated with any glioma subtype, is the only aberration we have detected in all adult malignancy grades of astrocytoma, is the most frequently observed aberration in tumors of malignancy grade II and III of this glial cell subtype, and appears to be specific to gliomas displaying solely astrocytic differentiation. Furthermore, these results indicate that the loss of chromosome 17p sequences most frequently involves mitotic recombination. As has been previously demonstrated with embryonal rhabdomyosarcoma (17), mitotic recombination mapping offers an approach toward high resolution subregional localization of loci involved in the evolution of specific tumors. The data presented here corroborate the value of this approach by revealing a region of the short arm distal to a marker in band p11.2 that attains common homozygosity for those astrocytomas losing genetic information on chromosome 17 and, thus, is inferred to harbor a locus or loci whose rearrangement is related to the development of these tumors.