Polysomy 7

Abstract: Amplification of the gene for epidermal growth factor receptor (EGFR) is a common finding in malignant gliomas. We found that 18 of 29 grade 3 and grade 4 gliomas had EGFR amplification when assayed using fluorescence in situ hybridization. The amplification pattern suggests that the amplicon is contained within double minute chromosomes in most cases. EGFR copy number can differ by 20-fold in amplified cells within a single case. Polysomy 7 occurs frequently in both EGFR-amplified and -unamplified cells. More than one-third of the cases had < or = 10 percent of cells with amplified EGFR, and it is likely that these cases would not have been identified by methods that do not examine DNA on a cell by cell basis.

Abstract: Chromosome analysis in a series of human glioblastoma cell lines (HeRo, HeRo-SV1, A172, T406, T508, T705) has indicated characteristic changes in the karyotype, the most striking and consistent of which is a significant increase in the copy number of chromosome 7, with up to 8 copies per metaphase. As determined by Spurr et al., chromosome 7 represents the genomic locus for the oncogene erbB (7pter-q22). Therefore, we have compared the number of chromosomes 7 to the levels of expression of the erbB oncogene. Interestingly, in all of them erbB-specific mRNA was found to be increased at levels even higher than expected from the number of chromosomes 7 found. In contrast, in an astrocytoma of slightly lower grade of malignancy (cell line T567), neither polysomy 7 nor significant expression of the erbB oncogene was noted.

Abstract: Cytogenetic analysis was performed on 16 primary tumors, 2 effusions, and 3 cell lines from 21 patients with non-small cell lung cancer (NSCLC). In 20 patients specimens were obtained prior to initiating cytotoxic therapy. Extensive clonal chromosome alterations were found in all cases. The most frequent numerical changes were polysomy 7 and polysomy 20 (each seen in 12 specimens). In addition, tumor cells from another six cases exhibited partial trisomy 7, with the shortest region of overlap (SRO) at 7p11–p13. Rearrangements of chromosomes 1, 3, 6, 8, 11, 15, 17, and 19 were each observed in nine or more tumors. Breakpoints were clustered at several chromosomal sites, including 1p13, 3p13, 15p11–q11, 17p11, and 19q13. Recurrent loss involving 1p, 3p, 6q, 11p, 15p, 17p, and 19q were each seen in at least eight cases. The SRO of 3p losses was at band 3p21. Double minute chromosomes were found in three tumors. Overall, our findings indicate that even though karyotypes in newly diagnosed NSCLC are very complex, recurrent cytogenetic changes can be identified. The high incidence of loss of 17p (14 of 21 specimens) appears to be compatible with reports implicating the TP53 gene (at band 17p13) as a frequent site for genetic alteration in lung cancer. Moreover, the recurrence of loss of 3p (12 cases) and 11p (10 cases) is also consistent with recent molecular evidence. The existence of other “hot spots” for cytogenetic change, particularly those involving specific regions on chromosomes 7, 15, and 19, warrants further molecular investigation of these sites in NSCLC.