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Table 2 Description of the 22 CpG islands used to establish the methylation classifier in oral rinse samples

From: CpG island methylation profile in non-invasive oral rinse samples is predictive of oral and pharyngeal carcinoma

M

CpG island coordinatesa

Number of CpGs covered by the array

Associated gene (ncRNA)

CpG island relationship to gene

Enhancer region

DNase hypersensitivity site

Associated gene functione

Differential methylation in oral/pharyngeal tumor tissuef

FDR-adjusted Q-value

Median differenceg (range)

1

chr3:15286143-15286274

3

SH3BP5

5′UTR: body

True

True

Inhibits phosphorylation activity of Bruton Agammaglobulinemia Tyrosine Kinase; may play a role in BCR-induced apoptosis

1.12E−07

−0.19 (−0.35, −0.04)

2

chr17:77848690-77848800

3

(JD529337)b

 

True

True

 

9.86E−09

−0.14 (−0.17, −0.07)

3

chr12:118725604-118725889

3

CIT

Body

True

 

Serine/threonine-protein kinase that plays a role in cell division/cytokinesis

3.04E−09

0.32 (0.13, 0.46)

4

chr1:154198084-154198623

3

ARHGEF2

Body

True

True

Plays a fundamental role in cellular processes initiated by extracellular stimuli via G protein coupled receptors

4.21E−09

−0.22 (−0.31, −0.01)

5

chr12:28015205-28015607

3

PTHLH

5′UTR (TSS1500)

  

Neuroendocrine peptide member of the parathyroid hormone family that is a critical regulator of cellular and organ growth, development, migration, differentiation, survival, and epithelial calcium ion transport

3.97E−06

−0.19 (−0.29, 0.37)

6

chr11:2511670-2512178

4

KCNQ1

Body

True

 

Voltage-gated potassium channel required for the repolarization phase of the cardiac action potential; exhibits tissue-specific imprinting

3.04E−09

−0.29 (−0.52, −0.10)

7

chr1:8194584-8194818

3

(JD505160)

 

True

True

 

1.40E−06

−0.13 (−0.26, 0.09)

8

chr12:110319267-110319654

4

(see footnote)c

    

1.12E−07

−0.04 (−0.06, 0.01)

9

chr5:161207831-161208167

4

GABRA1

5′UTR (TSS1500:TSS200)

  

Receptor for gamma-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the brain

5.08E−06

0.09 (−0.03, 0.66)

10

chr19:5538686-5538939

3

SAFB2

Body

  

Binds to scaffold/matrix attachment region (S/MAR) DNA; may function as an estrogen receptor corepressor or inhibitor of cell proliferation

0.00015

0.25 (−0.35, 0.27)

11

chr6:25135475-25135786

3

BC070382 d

    

3.04E−09

−0.29 (−0.47, −0.04)

12

chr10:134072408-134072501

3

PWWP2B

Body: 3′UTR

  

PWWP Domain-Containing Protein 2B

6.28E−08

0.21 (−0.10, 0.29)

13

chr1:10818517-10818704

3

  

True

True

 

0.00066

−0.16 (−0.28, 0.19)

14

chr1:1385949-1386143

5

ATAD3C

Body

  

ATPase Family AAA Domain-Containing Protein 3C

9.23E−08

−0.17 (−0.36, 0.03)

15

chr10:53743705-53744974

7

DKK1

5′UTR: Body

 

TRUE

Member of the dickkopf protein-coding gene family, which play an important role in vertebrate development

0.59

−0.02 (−0.10, 0.57)

16

chr11:20588323-20588561

3

SLC6A5

Body

True

 

Solute-carrier transporter involved in the clearance of extracellular glycine during glycine-mediated neurotransmission

3.51E−06

−0.03 (−0.06, 0.001)

17

chr10:134210902-134211265

5

INPP5A

Body

  

Membrane-associated type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphate that mobilizes intracellular calcium and acts as a second messenger for mediating cell responses to various stimuli

1.89E−07

−0.09 (−0.42, −0.0004)

18

chr5:10702368-10703458

3

ANKRD33B

Body

  

Ankyrin Repeat Domain-Containing Protein 33B

7.67E−09

0.14 (0.03, 0.18)

19

chr16:85998896-85999172

3

ZCCHC14

3′UTR

 

TRUE

Zinc Finger CCHC Domain-Containing Protein 14; interacts with nuclear transcription factors NFIC and NFIX

0.13

0.09 (−0.42, 0.20)

20

chr13:105827274-105827476

3

(LINC00460)

   

(long non-coding RNA of unknown function)

3.34E−08

−0.26 (−0.48, 0.04)

21

chr5:1010475-1010610

3

  

True

True

 

8.09E−05

−0.19 (−0.34, 0.11)

22

chr2:216945117-216945376

6

MARCH4

5′UTR (TSS1 500:TSS200)

  

E3 ubiquitin-protein ligase that may mediate ubiquitination of MHC-I and CD4, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies

0.00076

−0.04 (−0.06, 0.08)

  1. Abbreviations: M rank order of top CpG islands comprising the oral rinse methylation classifier, UTR untranslated region, kb kilobase, TSS200 within 200 bases of transcription start site, TSS1500 within 1500 bases of transcription start site, ncRNA non-coding RNA, FDR false discovery rate (Benjamini and Hochberg)
  2. aCoordinates correspond to CpG islands predicted by Hidden Markov Model (HMM) using the NCBI36/hg18 assembly
  3. bCpG island is <2 kb downstream of a bioinformatically detectable short RNA sequence
  4. cCpG island is <1 kb upstream (JD366788, JD497927, JD365992) and downstream (JD358111, JD476820, JD415033) of several bioinformatically detectable short RNA sequences
  5. dHypothetical short protein-coding sequence
  6. eGene function was extracted from GeneCards (www.genecards.org)
  7. fBased on Infinium HumanMethylation450 data from 34 tumor/matched-adjacent normal tissue pairs from The Cancer Genome Atlas (TCGA)
  8. gMedian difference in beta value of tumors relative to controls (positive value denotes relative hypermethylation; negative value denotes relative hypomethylation)