Therapeutic implications of cancer gene amplifications without mRNA overexpression: silence may not be golden

Table 1 Silencing distribution between focal and non-focal high-level amplifications (data from TCGA)

	Total number of high-level amplifications*	Tumor-to-normal differential RNA expression		Number of silenced** amplifications	Number of non-silenced amplifications	Chi-square p value
	N (%)	Mean [95% confidence interval]	T test p value	N (%)	N (%)	Chi-square p value
All genes (N = 18,870)
All amplifications	166,707 (100%)	+ 548 [+ 500 to + 595] %	–	9534 (6%)	157,173 (94%)	–
Focal amplifications	137,819 (83%)	+ 559 [+ 505 to + 613] %	0.296	6973 (4%)	130,846 (78%)	< 0.00001
Non-focal amplifications***	28,888 (17%)	+ 493 [+ 400 to + 585] %		2561 (2%)	26,328 (16%)
Cancer-related genes**** (N = 832)
All amplifications	8211 (100%)	+ 1084 [+ 742 to + 1426] %	–	485 (6%)	7726 (94%)	–
Focal amplifications	5612 (68%)	+ 1207 [+ 723 to + 1691] %	0.300	233 (3%)	5379 (66%)	< 0.00001
Non-focal amplifications	2599 (32%)	+ 818 [+ 549 to + 1088] %		252 (3%)	2347 (29%)

Numbers in bold represent statistically significant Chi-square p-values at the alpha level of 0.05, as well as the criteria that have the largest contribution to the Chi-square statistic
*Gene level amplification included those genes with ≥ 6 copies
**RNA silencing was defined by an 80% decrease of expression in the tumor sample compared to the normal sample, including only tumor samples that presented a high-level amplification for that gene (≥ 6 copies of the gene)
***Non-focal amplifications are co-amplification of genes that are located in the same 0.1 megabase genomic window
****Cancer-related genes are listed in Additional file 2: Table S2. The list of cancer-related genes was defined as the union of genes curated by the Cancer Gene Census (CGC) from the Catalogue of Somatic Mutations in Cancer (COSMIC) and genes analyzed by Foundation Medicine Inc. in their commercial panels Foundation One and Foundation One Heme (N = 946 distinct genes)

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