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In contrast, the average number of alterations in low/intermediate and high-grade IDC was similar, and although EGFR alterations were exclusively found in high-grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS.
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The CGH analyses of our series of adenomyoepithelial neoplasms support this idea, because a stepwise increase in the average number of genetic alterations was observed.
7p-gains were again predominantly present in a cluster characterised by a low average number of cytogenetic alterations and a significantly higher frequency of 16q-losses.
Ductal invasive grade 3 carcinomas with 7p-gains were mainly aneuploid, displayed 16q-losses in 71% of the cases and displayed a high average number of cytogenetic alterations.
Based on the CGH profiles and the average number of genomic alterations found in both types of lesion (2.9 in both), those investigators suggested that ALH and LCIS represent the same genetic stage of development.
Especially, the finding of a high average number of cytogenetic alterations, shown by itself to be a bad prognostic marker (Isola et al, 1995), and the association with 9q-losses (Gray, 2001) make this likely.
One of these major cluster arms (indicated by a frame in Figure 1) revealed a lower average number of genetic alterations per case (7.68±6.08 vs 8.97±5.96), and a significantly higher frequency of 16q-losses (P<0.001), 7p-gains (P<0.05) and combined 7p-gains/16q-losses (P<0.001).
We found almost twice the number of DNA gains than DNA losses (571 vs. 298) and the average number of copy number alterations (ANCA=total number of alterations in the sample collective/total number of cases) was 43.45 per case.
Cancer cell lines were not included in our analysis.> Of the 18 cancer types with at least six representative samples, mesothelioma and small-cell lung cancer had the greatest PGA and average number of copy number alterations (CNAs), suggesting that they may be the most genomically unstable in the context of CIN (Fig. 4).
On the average, 19.5 DNA losses and 20.7 gains were detected in the samples, with an average number of chromosomal aberrations of 40.2 alterations per case, ranging from 52 alterations in VIPA to 19 alterations in INBL.
Interestingly, in all tumour subtypes, including the sporadic group, which showed similar average numbers of both alterations, more genetic material was lost than gained.
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