Table 2.

Comparing frequency of mutated genes in samples with amplification burden in the top 10% of samples vs. those in the bottom 90% using WGS or the FM panel (see also Supplemental Table S1 for the FM gene list) for both TCGA and UCSD datasets.

Gene	Top 10% of amplifications	Bottom 90% of amplifications			Odds Ratio [CI95%]	Bonferroni adjusted p-value
TCGA dataset comparing frequency of mutated genes in samples with amplifications in the top 10% vs. those in the bottom 90% using WGS*
TP53****	449/727 (61.8%)		2448/6519 (37.6%)	2.7 [2.3–3.1]		<0.00001	TP53 alterations associated with increased amplifications while BRAF and KRAS alterations associated with decreased amplifications
BRAF	17/727 (2.3%)		591/6519 (9.1%)	0.2 [0.1–0.4]		<0.00001
KRAS	34/727 (4.7%)		611/6519 (9.4%)	0.5 [0.3–0.7]		0.008
GATA3	29/727 (4.0%)		159/6519 (2.4%)	1.7 [1.1–2.5]		Not significant
TCGA dataset comparing frequency of mutated genes in samples with amplifications in the top 10% vs. those in the bottom 90% using FM panel**
TP53	481/732 (65.7%)		2416/6514 (37.1%)	3.3 [2.8–3.8]		<0.003	TP53 alterations associated with increased amplifications while BRAF and KRAS alterations associated with decreased amplifications
BRAF	16/732 (2.2%)		592/6514 (9.1%)	0.2 [0.1–0.4]		<0.003
KRAS	25/732 (3.4%)		620/6514 (9.5%)	0.3 [0.2–0.5]		<0.003
GATA3	32/732 (4.4%)		156/6514 (2.4%)	1.9 [1.3–2.7]		Not significant
UCSD dataset comparing frequency of mutated genes in samples with amplifications in the top 10% vs. those in the bottom 90% using FM panel***
TP53	117/185 (63.2%)	707/1706 (41.4%)			2.4 [1.8–3.3]	<0.003	TP53 alterations associated with increased amplifications
BRAF	4/185 (2.2%)	107/1706 (6.3%)			0.3 [0.1–0.9]	Not significant
KRAS	32/185 (17.3%)	259/1706 (15.2%)			1.2 [0.8–1.7]	Not significant
GATA3	11/185 (5.9%)	35/1706 (2.1%)			3.0 [1.5–6.0]	Not significant

*Using the TCGA cohort, which consists of 7,246 cancer samples, the 90^th percentile for number of amplifications using WGS was calculated to be 1,016. The 90^th percentile for number of amplifications using the FM panel was calculated to be 15.

** The FM panel includes 321 genes (see supplemental Table S1).

*** Using the UCSD dataset, which consists of 1,891 cancer samples, the 90^th percentile for number of amplifications (FM panel) was calculated to be 9.

**** Refers to number of samples with designated gene mutation/total samples in that subgroup. For instance, within TCGA database, 727 samples were in the top 10% for amplification burden (“amplificators”); of these 727 samples, 449 (65.7%) had a TP53 mutation.

Abbreviations: FM = Foundation Medicine; TCGA = The Cancer Genome Atlas; UCSD = University of California San Diego; WGS = whole genome sequencing.