Mitotic recombination of chromosome 17 in astrocytomas.

Abstract

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.

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

“…Hot-spots for genomic alteration have been described for various tumors 35,36 and may include genes affecting pathways common to cancer biology such as cell cycle regulation, mechanisms of invasion, and metastasis. For instance, several regions of chromosome 1p, including 1p36 and 1p22, have been implicated in the tumorigenesis of a wide range of malignancies.…”

PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers

“…SCLC and NSCLC tumor cell lines were obtained from Dr Dean Edwards of the University of Colorado Cancer Center Tissue Culture Core and Dr Adi F Gazdar of University of Texas, Southwestern Medical Center. DNA from each sample were isolated and puri®ed as previously reported (James et al, 1988). Tumor tissues of NSCLC were obtained from the patients diagnosed and operated at the Mayo Clinic (Rochester, MN).…”

A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors

“…Rearrangement and loss of at least some parts of the second copy of chromosome 10, especially in the 10q23 ± 26 region, has been demonstrated in approximately 80% of glioblastoma multiforme (GBM) tumors (Bigner and Vogelstein, 1990;James et al, 1988;Karlbom et al, 1993;Rasheed et al, 1992). These changes are rarely seen in low-grade gliomas.…”