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Table 2 Gene regions with FDR-adjusted p value for Spearman correlations of average gene region methylation with log(IC50) of antitumor agents < 0.1

From: Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets

Agent

Inhibitor category

Associated gene

Gene region

Cytoband

Number of probes in gene region

ρ for average region methylation vs log(IC50)

pFDR for average region methylation vs log(IC50)

Highest |r| for expression vs log(IC50)

Lowest p for expression vs log(IC50)

Highest |ρ| for expression vs region methylation

Lowest p for expression vs average region methylation

Transcript with lowest p for expression vs log(IC50)

ABT-348

Aurora kinase

CEP350

UTR3

1q25.2

1

0.6096

0.0953

0.0270

0.8281

− 0.1887

0.1292

NM_014810 (CEP350)

ABT-737

Bcl-2

TCERG1L

UTR3

10q26.3

6

− 0.6251

0.0787

− 0.5740

3.81 × 10−7

0.6026

8.64 × 10−8

NM_174937 (TCERG1L)

AZD-1152

Aurora kinase

MLPH

UTR3

2q37.3

1

0.6148

0.0905

0.3014

0.0132

0.5396

2.94 × 10-6

NM_024101 (MLPH)

BAL-101553

Tubulin fragmenter

STARD3

UTR3

17q12

5

0.6154

0.0905

0.0754

0.5440

− 0.0173

0.8900

NM_006804 (STARD3)

BI-2536

PLK-1

MLPH

UTR3

2q37.3

1

0.6172

0.0905

0.2486

0.0425

0.5396

2.94 × 10-6

NM_024101 (MLPH)

BIA

GSK-3

TTC15

TSS200

2p25.3

4

0.6138

0.0905

− 0.1191

0.3372

− 0.1668

0.1807

NM_016030 (TTC15)

BIM-46187

Pan-G-protein

C8orf74

UTR5

8p23.1

1

− 0.6721

0.0145*

     

BIM-46187

Pan-G-protein

C8orf74

Exon 1

8p23.1

1

− 0.6721

0.0145*

     

BIM-46187

Pan-G-protein

C8orf74

TSS200

8p23.1

3

− 0.6459

0.0530

     

Depsipeptide

HDAC

MTERFD3

Gene body

12q23.3

1

− 0.6468

0.0530

0.1686

0.1725

− 0.3133

0.0104

NM_001033050 (MTERFD3)

Flavopiridol

CDK

SEC11C

TSS1500

18q21.32

4

0.6180

0.0905

0.0731

0.5566

0.5476

1.95 × 10-6

NM_033280 (SEC11C)

GSK-461364

PLK-1

LOC100128568

Gene body

19p13.3

20

0.6267

0.0787

     

Sapanisertib

mTOR

SPG20

UTR5

13q13.3

28

0.6252

0.0787

− 0.3122

0.0101

− 0.5423

2.55 × 10−6

NM_001142295 (SPG20)

Ivacaftor

 

MIF

TSS200

22q11.23

6

0.6144

0.0905

− 0.2685

0.0280

− 0.4318

0.0003

NM_002415 (MIF)

Ivacaftor

 

RPUSD2

Exon 1

15q15.1

4

0.6127

0.0913

− 0.0729

0.5575

− 0.0908

0.4683

NM_152260 (RPUSD2)

ONX-0912

Proteasome

CYP11B2

Gene body

8q24.3

1

− 0.6078

0.0992

− 0.1414

0.2536

0.1705

0.1711

NM_000498 (CYP11B2)

R-547

CDK

GIGYF2

TSS1500

2q37.1

4

0.6354

0.0639

− 0.1255

0.3114

− 0.1525

0.2215

NM_001103147 (GIGYF2)

R-547

CDK

KCNH6

UTR5

17q23.3

4

0.6409

0.0607

0.0677

0.5861

0.1664

0.1818

NM_030779 (KCNH6)

R-547

CDK

TREX1

Exon 1

3p21.31

9

− 0.6119

0.0913

     

R-547

CDK

TREX1

UTR5

3p21.31

6

− 0.6109

0.0913

     

SC-1

Ras-GAP

WT1

UTR3

11p13

1

− 0.6372

0.0639

− 0.3245

0.0074

0.4004

0.0009

NM_024424 (WT1)

SCH-1473759

Aurora kinase

ITPA

UTR3

20p13

1

− 0.6110

0.0913

0.0138

0.9115

− 0.0562

0.6537

NM_033453 (ITPA)

SNS-314

Aurora kinase

CEP350

UTR3

1q25.2

1

0.6280

0.0787

− 0.0704

0.5713

− 0.1887

0.1292

NM_014810 (CEP350)

TAK-901

Aurora kinase

TREX1

Exon 1

3p21.31

9

− 0.6231

0.0796

     

TAK-901

Aurora kinase

TREX1

UTR5

3p21.31

6

− 0.6088

0.0969

     

TAK-960 analog

PLK-1

GLYATL1

TSS1500

11q12.1

2

0.6164

0.0905

0.1228

0.3223

0.4304

0.0003

NM_080661 (GLYATL1)

Vertex ATR inhibitor Cpd 45

ATR

TREX1

Exon 1

3p21.31

9

− 0.6244

0.0787

     

Vertex ATR inhibitor Cpd 45

ATR

TREX1

UTR5

3p21.31

6

− 0.6182

0.0905

     
  1. Correlation results of log2 of expression of the most strongly correlated transcript with gene region methylation and with log(IC50) are provided for those genes that had matching transcript data in the Affymetrix GeneChip®Human Exon 1.0 ST Array. Number of probes in gene region provides the number of probes annotated by the Illumina Infinium MethylationEPIC BeadChip manifest annotation [18] according to the UCSC genome browser as belonging to a particular gene region; methylation beta-values of all such probes were combined to compute the average region methylation value. pFDR p value adjusted for false discovery rate, accounting for all 412 drug agents with variable drug response and 108,795 gene regions
  2. *pFDR < 0.05
  3. ρ Spearman correlation coefficient, r Pearson correlation coefficient, ATR ataxia telangiectasia and Rad3-related protein, CDK cyclin-dependent kinase, GSK-3 glycogen synthase kinase 3, PLK-1 polo-like kinase 1
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Clinical Epigenetics

ISSN: 1868-7083

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