AMPLIFICATION OF THE 11Q13 REGION IN HUMAN CARCINOMA CELL-LINES - A MECHANISTIC VIEW

We previously proposed that a local duplication, not the loss of the s ubsequently amplified marker from its original site, might be the firs t step in gene amplification in human cells. It is important to invest igate this issue in naturally occurring amplification and when copy nu mbers are relatively low. We have examined the location of single-copy and amplified 11q13 sequences in cell lines from human breast cancers and squamous cell carcinomas using fluorescence in situ hybridization both with a probe specific for the 11q13 amplifying region and with a chromosome 11-specific library. We show that in most cell lines the 1 1q13 amplicons are physically linked to chromosome II or to a chromoso me derived from chromosome 11 by various rearrangements near the 11q13 region. In none of the cell lines were interstitial deletions of 11q1 3 detected. These results indicate that 11q13 amplification in human t umor cells generally does not involve deletion as the initial step. On e cell line with chromosomally located amplified 11q13 sequences conta ined double minutes that harbored the MYC gene but no 11q13 sequences. This suggests that the genetic outcome and the mechanism of gene ampl ification are probably dependent on specific DNA sequences rather than on the origin of the cells.