Novel genetic targets in endometrial cancer

Figures & data

Table 1. Mutation frequency of novel significantly mutated protein-encoding genes identified among serous and non-ultramutated endometrioid ECs.

Gene symbol	Frequency of somatic mutations*						Ref.
	Histological subtype		Molecular subgroup [7]
	Endometrioid (%)	Serous (%)	Ultramutated (%)	Hypermutated/MSI (%)	Copy number low/MSS (%)	Copy number high/serous-like (%)
ARID5B	9 – 18	0	47	23	6	0	[6,7]
BCOR	4 – 10	0	65	17	7	0	[6,7]
CHD4	7 – 13	13 – 18	65	6	12	13	[3,4,6,7]
CSDE1	7	0	59	15	1	0	[7]
CTCF	15 – 29	0	41	23	21	0	[6,7,9]
FBXW7	7 – 27	20 – 29	82	9	6	22	[2-4,6,7]
GIGYF2	8 – 14	6	59	20	0	7	[6,7]
HIST1H2BD	2	0	0	8	1	0	[7]
LIMCH1	6 – 9	0	53	12	0	0	[6,7]
MECOM	4	0	24	5	4	0	[7]
METTL14	3	0	24	5	3	0	[7]
NKAP	4	0	18	11	1	0	[6,7]
RBMX	4	0	24	12	0	0	[7]
RPL22	10 – 52	0	29	37	0	0	[7,21]
SGK1	4	2	35	3	6	2	[7]
SOX17	2	0	0	0	8	0	[7]
SPOP	0 – 6	4 – 8	29	6	10	5	[3,4,6,7]
TAF1	11 – 27	4 – 9	82	25	1	5	[4,6,7]
TNFAIP6	2	0	29	2	1	0	[7]
ZFHX3	13 – 36	6	82	31	2	7	[6,7]

CSMD3 is a novel SMG in EC but is not shown in Table 1 because it may be a false-positive.

MIR1277 is significantly mutated but is not shown in Table 1 because it is not a protein-encoding gene.

*Mutation frequencies for the TCGA dataset were obtained from Kandoth et al. [7] and via the cBioPortal for Cancer Genomics [32,33].

MSI: Microsatellite instability; MSS: Microsatellite stable; SMG: Significantly mutated gene; TCGA: The Cancer Genome Atlas.

Table 2. Statistically significant trends in mutation patterns* involving novel SMGs identified in non-ultramutated ECs in the TCGA study [7].

Molecular subgroup	Gene pair	Trend in mutation pattern*	p-value*
Hypermutated/MSI	ARID5B-ZFHX3	Co-occurrence	0.035
	CTCF-FGFR2	Co-occurrence	0.025
	FBXW7-LIMCH1	Co-occurrence	0.021
	BCOR- PPP2R1A	Co-occurrence	0.006
	HIST1H2BD -RPL22	Co-occurrence	0.005
	SPOP-RPL22	Co-occurrence	0.016
	SPOP-CCND1	Co-occurrence	0.005
	SPOP-PPP2R1A	Co-occurrence	0.040
	MECOM-PPP2R1A	Co-occurrence	0.021
	MECOM-ATR	Co-occurrence	0.0004
	METTL14-FGFR2	Co-occurrence	0.048
	METTL14-PPP2R1A	Co-occurrence	0.021
	SGK1-RBMX	Co-occurrence	0.013
	TNFAIP6-MECOM	Co-occurrence	0.046
	TNFAIP6-METTL14	Co-occurrence	0.046
Copy number low/MSS	SPOP-PTEN	Mutual exclusivity	0.029
	SOX17-CTNNB1	Mutual exclusivity	0.043
	FBXW7-CTNNB1	Mutual exclusivity	0.022
	FBXW7-SOX17	Co-occurrence	0.047
	MECOM-PIK3R1	Co-occurrence	0.011
Copy number high/serous-like	CHD4-FBXW7	Co-occurrence	0.009
	GIGYF2-TP53	Mutual exclusivity	0.001
Ultramutated	ZFHX3-PIK3CA	Co-occurrence	0.015
	ZFHX3-ATR	Co-occurrence	0.029
	GIGYF2-CSDE1	Co-occurrence	0.004
	SGK1-CTNNB1	Co-occurrence	0.017
	ATR-CTNNB1	Co-occurrence	0.017
	CSDE1-FGFR2	Co-occurrence	0.041
	GIGYF2-FGFR2	Co-occurrence	0.041
	LIMCH1-PPP2R1A	Co-occurrence	0.020
	SPOP-KRAS	Mutual exclusivity	0.009
	RBMX-KRAS	Mutual exclusivity	0.029
	CCND1-RPL22	Co-occurrence	0.014

SMGs identified in the ultramutated subgroup were not included in the input query. Only gene-pairs demonstrating a p-value < 0.05, as derived via Fisher's exact test, are shown; p-values are not adjusted for false discovery rate.

*Data were obtained from the cBioCancer Genomics Portal [32,33].

MSI: Microsatellite instability; MSS: Microsatellite stable; SMGs: Significantly mutated genes; TCGA: The Cancer Genome Atlas.

Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497:67-73

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