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mors, respectively (Figs. 1D-F, K and L, and 4A and B). One such image appeared to show co-amplification of the ERBB2
sequence with Ferrostatin 1 17; this image is of particular inter-est because balanced increases in the numbers of ERBB2 and centromere 17 would have been interpreted as polysomy 17 by the 2007 criteria and so would have been excluded as a po-tential target of trastuzumab. However, more recent criteria suggest that increases in centromere-17 copy number may not necessarily represent chromosome-17 polysomy but instead may correspond to gain or amplification of the chromosome-17 centromeric region . The present study suggested that gene amplification associated with centromeric regions may be a common type of amplification event, occurring as a subset of nearly all common amplifications.
Amplicons in breast cancers 43
Based the previous studies delineating the boundaries of the amplicons, common initial break sites in the amplicons are known to correspond to specific genes. Initially, genes lo-cated near each other in a chromosome region are co-amplified physically, but the amplicons of advanced cancers selected during tumor development may not be the same as the original amplicons, as shown in Fig. 2. In the present study, the pre-dominant type of amplicon found at 8p, 11q, and 17q was HSR, although 83% (26/31) of MYC amplifications occurred in non-HSR types. Marotta et al found neither duplicated seg-ments nor fragile sites within the 6-Mb region surrounding the MYC oncogene , suggesting a different mechanism for MYC amplification.
In the current study, co-amplifications of the non-syntenic genes were observed in 35 tumors, as shown in Table 2. In each of eight of these tumors, the non-syntenic genes consti-tuted a single amplification unit (and thus a larger amplicon). Specifically, these events included the amplicons on 8p11 and 11q13 in six tumors; the amplicons on 8p11 and 17q11–
12 in one case; and co-amplification of 17q11–12 and 16q22.1 in another case. The FISH images of intermingling of these non-syntenic genes in single clusters suggests to us that these events correspond to the early fusion of both genes by translocation, with subsequent amplification by BFB cycle.
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