Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

Inchanalkar, Mayuri; Srivatsa, Sumana; Ambatipudi, Srikant; Bhosale, Priyanka G.; Patil, Asawari; Schäffer, Alejandro A.; Beerenwinkel, Niko; Mahimkar, Manoj B.

doi:10.1186/s13148-023-01510-z

Clinical Epigenetics

Table 2 List of candidate prognostic markers based on methylation and CNA data

From: Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

Sr no	Cytoband	Genes	Alteration	Promoter status	MethCNA annotation	∆β	Rnbeads adjusted FDR	CNAmet FDR	LASSO Coefficients
1	1p34.3	AGO1	Gain	Hypo	Loss tendency*	− 0.13040191	9.92E−08	0	0.02357709
2	9p13.3	ARHGEF39	Hyper	Hyper	Not available	0.15826579	4.79E−11	0.07915789	5.406079817
3	1q23.1	CD1C	Hypo	Hypo	Not available	− 0.10967453	0.00000036	0.025	− 5.86758818
4	7q21.13	CLDN12	Gain	Hypo	Gain	− 0.20024732	3.01E−10	0.07425	− 0.17467983
5	20p11.21	*CST7*	Gain	Hypo	Gain	− 0.18512047	3.09E−17	0.07826087	0.7816124
6	18q22.3	*CYB5A*	Loss	Hyper	Loss	0.154479225	0.00000204	0	− 0.2566186
7	9q34.11	DPM2	Gain	Hyper	Gain	0.110067901	3.95E−09	0.01342857	0.020726005
8	10p14	ECHDC3	Loss	Hyper	Loss	0.102629326	0.000083	0.051625	0.2538569
9	4q35.2	FAT1^#	Hypo	Hypo	Hyper	− 0.10716469	2.15E−09	0	− 8.91100971
10	2p22.2	FEZ2	Gain	Hypo	No effect	− 0.12593147	0.00000482	0.07772727	− 0.09276379
11	2p22.2	FEZ2	Hypo	Hypo	No effect	− 0.12593147	0.00000482	0.07772727	− 0.42588184
12	5p13.1-p12	*GHR*	Gain	Hypo	Gain	− 0.12027275	9.11E−13	0	0.49366068
13	9p24.1	GLDC^#	Hyper	Hyper	Hyper	0.11272417	0.000540999	0.02145455	1.043842
14	17q21.32	HOXB13^#	Hyper	Hyper	Hyper	0.101298897	0.000789507	0	3.113007
15	19p13.11	JAK3	Hyper	Hyper	Hyper	0.106127081	0.0000126	0.06807692	8.206031
16	2p23.3	KRTCAP3	Hyper	Hyper	Hyper	0.103330448	0.00000192	0.00680769	1.10005
17	1p34.1	LURAP1	Loss	Hyper	Not available	0.115584283	0.00000258	0	0.03147996
18	2q24.2	*LY75*	Loss	Hyper	Loss tendency*	0.154711559	0.00000465	0	− 0.3404406
19	9q34.3	MAMDC4	Hyper	Hyper	Not available	0.103718753	1.66E−12	0	0.9015477
20	5q33.3	MED7	Hypo	Hypo	Hyper	− 0.10052829	0.000350364	0.047	− 0.22621307
21	1q21.3	MLLT11	Hyper	Hyper	Hyper	0.1010586	0.0000537	0.06042857	0.331861046
22	1q21.3	*MLLT11*	Gain	Hyper	Gain	0.1010586	0.0000537	0.06042857	0.599877098
23	6q23.2	TAAR5	Hypo	Hypo	Not available	− 0.10711508	0.00000875	0.06266667	− 5.26569245
24	2q24.2	TANK	Gain	Hyper	Loss tendency*	0.127622181	0.00000758	0	− 0.42285359
25	13q14.2	TRIM13	Hyper	Hyper	Hyper	0.104869077	0.000000876	0.08952381	1.044432765
26	3q23	U2SURP	Gain	Hyper	Not available	0.178676248	9.68E−11	0	− 0.16037072
27	19q13.41	ZNF83	Loss	Hyper	Gain tendency*	0.165017242	3.09E−11	0.04895745	2.93189E−16
28	19q13.41-q13.42	ZNF160	Loss	Hyper	Gain tendency*	0.284229499	1.28E−15	0.06726	0.0111227
29	19q13.42	ZNF331	Loss	Hyper	Gain tendency*	0.218690004	2.06E−15	0.0122069	6.15697E−15
30	19q13.41	ZNF350	Loss	Hyper	Gain tendency*	0.137293195	0.000000187	0.0122069	0.4037165
31	19q13.41	ZNF350	Hyper	Hyper	Hyper	0.137293195	0.000000187	0.0122069	− 2.244252
32	7p22.1	ZNF853	Gain	Hyper	Gain	0.156897804	4.03E−10	0.0282	0.025609823

The predictors (gene promoter methylation patterns and gene copy number alteration) are outlined by the gene symbol and alteration columns. The MethCNA annotation column summarises the alterations observed in TCGA head and neck squamous cell carcinoma (HNSCC) according to the MethCNA database
*The difference between the observed frequencies of both loss and gain is small in the MethCNA database for these genes
^#Target gene promoter selected for validation using bisulfite pyrosequencing; genes represented in bold were selected for copy number analysis using TaqMan real time PCR

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ISSN: 1868-7083

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