shc2416.58319p13.3 shc (src homology 2 domain containing) transforming protein 2...

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SHC2 416.58 3 19p13 .3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34 531.73 3 19p13 .3 cell division cycle 34 GZMM 544.03 4 19p13 .3 granzyme M (lymphocyte met-ase 1) BSG 572.45 4 19p13 .3 basigin (Ok blood group) FGF22 639.92 6 19p13 .3 fibroblast growth factor 22 RNF126 647.52 6 19p13 .3 ring finger protein 126 FSTL3 676.38 9 19p13 follistatin-like 3 (secreted glycoprotein) PTBP1 797.39 2 19p13 .3 polypyrimidine tract binding protein 1 AZU1 827.83 1 19p13 .3 azurocidin 1 PRTN3 840.98 5 19p13 .3 proteinase 3 ELANE 852.29 1 19p13 .3 elastase, neutrophil expressed KISS1R 917.34 2 19p13 .3 KISS1 receptor ARID3A 926.03 7 19p13 .3 AT rich interactive domain 3A (BRIGHT- like) TMEM2 59 1009.6 50 19p13 .3 transmembrane protein 259 HMHA1 1065.9 22 19p13 .3 histocompatibility (minor) HA-1 POLR2E 1086.5 78 19p13 .3 polymerase (RNA) II (DNA directed) polypeptide E, 25kDa GPX4 1103.9 36 19p13 .3 glutathione peroxidase 4 STK11 1205.7 98 19p13 .3 serine/threonine kinase 11 CIRBP 1269.2 67 19p13 .3 cold inducible RNA binding protein EFNA2 1286.1 53 19p13 ephrin-A2 MUM1 1354.9 76 19p13 .3 melanoma associated antigen (mutated) 1 DAZAP1 1407.5 84 19p13 .3 DAZ associated protein 1 RPS15 1438.3 63 19p13 .3 ribosomal protein S15 APC2 1450.1 48 19p13 .3 adenomatosis polyposis coli 2 PCSK4 1481.4 27 19p13 .3 proprotein convertase subtilisin/kexin type 4 REEP6 1491.1 65 19p13 .3 receptor accessory protein 6 PLK5 1524.0 73 19p13 .3 polo-like kinase 5 MEX3D 1554.6 68 19p13 .3 mex-3 homolog D (C. elegans) MBD3 1576.6 78 19p13 methyl-CpG binding domain protein 3 TCF3 1609.2 89 19p13 .3 transcription factor 3 ATP8B3 1782.0 74 19p13 .3 ATPase, aminophospholipid transporter, class I, type 8B, member 3 CSNK1G 2 1941.1 19p13 .3 casein kinase 1, gamma 2 SPPL2B 2328.62 9 19p13.3 signal peptide peptidase like 2B TIMM13 2425.62 2 19p13.3 translocase of inner mitochondrial membrane 13 homolog (yeast) GADD45B 2476.12 3 19p13.3 growth arrest and DNA-damage- inducible, beta GNG7 2511.21 8 19p13.3 guanine nucleotide binding protein (G protein), gamma 7 DIRAS1 2714.56 5 19p13.3 DIRAS family, GTP-binding RAS-like 1 SLC39A3 2732.52 3 19p13.3 solute carrier family 39 (zinc transporter), member 3 SGTA 2754.71 2 19p13 small glutamine-rich tetratricopeptide repeat (TPR)- containing, alpha TLE6 2977.53 6 19p13.3 transducin-like enhancer of split 6 (E(sp1) homolog, Drosophila) AES 3052.90 8 19p13.3 amino-terminal enhancer of split GNA11 3094.40 8 19p13.3 guanine nucleotide binding protein (G protein), alpha 11 (Gq class) GNA15 3136.19 1 19p13.3 guanine nucleotide binding protein (G protein), alpha 15 (Gq class) S1PR4 3178.73 6 19p13.3 sphingosine-1-phosphate receptor 4 NFIC 3366.56 5 19p13.3 nuclear factor I/C (CCAAT-binding transcription factor) DOHH 3490.81 9 19p13.3 deoxyhypusine hydroxylase/monooxygenase FZR1 3522.95 4 19p13.3 fizzy/cell division cycle 20 related 1 (Drosophila) HMG20B 3572.94 3 19p13.3 high mobility group 20B TBXA2R 3594.50 4 19p13.3 thromboxane A2 receptor CACTIN 3610.62 7 19p13.3 cactin, spliceosome C complex subunit PIP5K1C 3630.17 9 19p13.3 phosphatidylinositol-4-phosphate 5-kinase, type I, gamma MATK 3777.96 7 19p13.3 megakaryocyte-associated tyrosine kinase NMRK2 3933.10 1 19p13.3 nicotinamide riboside kinase 2 DAPK3 3958.45 2 19p13.3 death-associated protein kinase 3 MIR637 3961.41 2 19p13.3 microRNA 637 EEF2 3976.05 4 19p13.3 eukaryotic translation elongation factor 2 PIAS4 4007.74 9 19p13.3 protein inhibitor of activated STAT, 4 ZBTB7A 4045.21 6 19p13.3 zinc finger and BTB domain containing 7A MAP2K2 4090.32 0 19p13.3 mitogen-activated protein kinase kinase 2 SIRT6 4174.10 6 19p13.3 sirtuin 6 EBI3 4229.54 0 19p13 Epstein-Barr virus induced 3 ist of genes in human melanoma 19p13.3 focal deletion Liu et al. Supplementary Figur

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Page 1: SHC2416.58319p13.3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34531.73319p13.3cell division cycle 34 GZMM544.03419p13.3granzyme M

SHC2 416.583 19p13.3 SHC (Src homology 2 domain containing) transforming protein 2

CDC34 531.733 19p13.3 cell division cycle 34

GZMM 544.034 19p13.3 granzyme M (lymphocyte met-ase 1)

BSG 572.454 19p13.3 basigin (Ok blood group)FGF22 639.926 19p13.3 fibroblast growth factor 22RNF126 647.526 19p13.3 ring finger protein 126

FSTL3 676.389 19p13 follistatin-like 3 (secreted glycoprotein)

PTBP1 797.392 19p13.3 polypyrimidine tract binding protein 1

AZU1 827.831 19p13.3 azurocidin 1PRTN3 840.985 19p13.3 proteinase 3

ELANE 852.291 19p13.3 elastase, neutrophil expressed

KISS1R 917.342 19p13.3 KISS1 receptor

ARID3A 926.037 19p13.3 AT rich interactive domain 3A (BRIGHT-like)

TMEM259

1009.650 19p13.3 transmembrane protein 259

HMHA1 1065.922 19p13.3 histocompatibility (minor) HA-1

POLR2E 1086.578 19p13.3 polymerase (RNA) II (DNA directed) polypeptide E, 25kDa

GPX4 1103.936 19p13.3 glutathione peroxidase 4STK11 1205.798 19p13.3 serine/threonine kinase 11

CIRBP 1269.267 19p13.3 cold inducible RNA binding protein

EFNA2 1286.153 19p13 ephrin-A2

MUM1 1354.976 19p13.3 melanoma associated antigen (mutated) 1

DAZAP1 1407.584 19p13.3 DAZ associated protein 1RPS15 1438.363 19p13.3 ribosomal protein S15

APC2 1450.148 19p13.3 adenomatosis polyposis coli 2

PCSK4 1481.427 19p13.3 proprotein convertase subtilisin/kexin type 4

REEP6 1491.165 19p13.3 receptor accessory protein 6PLK5 1524.073 19p13.3 polo-like kinase 5

MEX3D 1554.668 19p13.3 mex-3 homolog D (C. elegans)

MBD3 1576.678 19p13 methyl-CpG binding domain protein 3

TCF3 1609.289 19p13.3 transcription factor 3

ATP8B3 1782.074 19p13.3 ATPase, aminophospholipid transporter, class I, type 8B, member 3

CSNK1G2

1941.161 19p13.3 casein kinase 1, gamma 2

BTBD2 1985.447 19p13.3-p12 BTB (POZ) domain containing 2

MKNK2 2037.470 19p13.3 MAP kinase interacting serine/threonine kinase 2

AP3D1 2100.987 19p13.3 adaptor-related protein complex 3, delta 1 subunit

DOT1L 2164.148 19p13.3 DOT1-like histone H3K79 methyltransferase

AMH 2249.113 19p13.3 anti-Mullerian hormone

OAZ1 2269.520 19p13.3 ornithine decarboxylase antizyme 1

SPPL2B 2328.629 19p13.3 signal peptide peptidase like 2B

TIMM13 2425.622 19p13.3 translocase of inner mitochondrial membrane 13 homolog (yeast)

GADD45B 2476.123 19p13.3 growth arrest and DNA-damage-inducible, beta

GNG7 2511.218 19p13.3 guanine nucleotide binding protein (G protein), gamma 7

DIRAS1 2714.565 19p13.3 DIRAS family, GTP-binding RAS-like 1

SLC39A3 2732.523 19p13.3 solute carrier family 39 (zinc transporter), member 3

SGTA 2754.712 19p13 small glutamine-rich tetratricopeptide repeat (TPR)-containing, alpha

TLE6 2977.536 19p13.3 transducin-like enhancer of split 6 (E(sp1) homolog, Drosophila)

AES 3052.908 19p13.3 amino-terminal enhancer of split

GNA11 3094.408 19p13.3 guanine nucleotide binding protein (G protein), alpha 11 (Gq class)

GNA15 3136.191 19p13.3 guanine nucleotide binding protein (G protein), alpha 15 (Gq class)

S1PR4 3178.736 19p13.3 sphingosine-1-phosphate receptor 4

NFIC 3366.565 19p13.3 nuclear factor I/C (CCAAT-binding transcription factor)

DOHH 3490.819 19p13.3 deoxyhypusine hydroxylase/monooxygenase

FZR1 3522.954 19p13.3 fizzy/cell division cycle 20 related 1 (Drosophila)

HMG20B 3572.943 19p13.3 high mobility group 20BTBXA2R 3594.504 19p13.3 thromboxane A2 receptor

CACTIN 3610.627 19p13.3 cactin, spliceosome C complex subunit

PIP5K1C 3630.179 19p13.3 phosphatidylinositol-4-phosphate 5-kinase, type I, gamma

MATK 3777.967 19p13.3 megakaryocyte-associated tyrosine kinase

NMRK2 3933.101 19p13.3 nicotinamide riboside kinase 2

DAPK3 3958.452 19p13.3 death-associated protein kinase 3

MIR637 3961.412 19p13.3 microRNA 637

EEF2 3976.054 19p13.3 eukaryotic translation elongation factor 2

PIAS4 4007.749 19p13.3 protein inhibitor of activated STAT, 4

ZBTB7A 4045.216 19p13.3 zinc finger and BTB domain containing 7A

MAP2K2 4090.320 19p13.3 mitogen-activated protein kinase kinase 2

SIRT6 4174.106 19p13.3 sirtuin 6EBI3 4229.540 19p13 Epstein-Barr virus induced 3

List of genes in human melanoma 19p13.3 focal deletion

Liu et al. Supplementary Figure S1

Page 2: SHC2416.58319p13.3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34531.73319p13.3cell division cycle 34 GZMM544.03419p13.3granzyme M

Rank

19p13.3 Gene Name

Gene Description Probe

Fold Change

P Value

1 CFD

complement factor D (adipsin) 205382_s_at

0.0830661

1.90E-10

2GNA15

guanine nucleotide binding protein (G protein), alpha 15 (Gq class) 205349_at

0.2489184

5.50E-06

3STAP2

signal transducing adaptor family member 2 221610_s_at

0.3297773

4.30E-09

4 INSR insulin receptor 213792_s_at0.3963676

6.30E-06

5SH2D3A

SH2 domain containing 3A 219513_s_at

0.4067233

5.50E-08

6MKNK2

MAP kinase interacting serine/threonine kinase 2 218205_s_at

0.4151389

0.00076

7ZBTB7A

zinc finger and BTB domain containing 7A 219186_at

0.4241946

4.90E-07

Rank

19p13.3 Gene Name

Gene Description Probe

Fold Change

P Value

1 C3complement component 3 217767_at

0.011325

1.80E-19

2 CFD

complement factor D (adipsin) 205382_s_at

0.0120048

7.30E-13

3GADD45B

growth arrest and DNA-damage-inducible, beta 207574_s_at

0.1937984 0.0004

4 ELANE

elastase, neutrophil expressed 206871_at

0.2427184 0.008

5GADD45B

growth arrest and DNA-damage-inducible, beta 209304_x_at

0.2785515 0.001

6ZBTB7A

zinc finger and BTB domain containing 7A 213303_x_at

0.2881844

0.000028

7ANGPTL4

angiopoietin-like 4 221009_s_at

0.3003003 0.0025

A BTalantov datasetKabbarah dataset

Liu et al. Supplementary Figure S2

Page 3: SHC2416.58319p13.3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34531.73319p13.3cell division cycle 34 GZMM544.03419p13.3granzyme M

Rank Probe set

Gene Symbol fold change P value

1 1456137_at NRXN3 4.92 0.222497

2 1416357_a_at MCAM 3.43 0.014862

3 1424067_at ICAM1 3.06 0.10178

4 1438193_at NRXN3 2.97 0.11258

5 1458652_at CD8B 2.5 0.601338

6 1417597_at CD28 2.33 0.021032

7 1445388_at CD226 2.3 0.439999

8 1416072_at CD34 1.98 0.016671

9 1436482_a_at SDC3 1.89 0.267842

10 1421966_at NCAM1 1.87 0.699974

11 1455143_at NLGN2 1.85 0.082354

12 1436568_at JAM2 1.82 0.044304

13 1420841_at PTPRF 1.76 0.158278

14 1433788_at NRXN3 1.75 0.126968

15 1450295_s_at PVR 1.74 0.17447

16 1449408_at JAM2 1.72 0.01615

17 1423903_at PVR 1.7 0.08544

18 1449906_at SELP 1.69 0.286053

19 1439629_at NRXN3 1.65 0.429062

A B

*

*

*

*

*

Rank NAME SIZE NES FDR q-val

1 KEGG_GALACTOSE_METABOLISM 45 2.274074 0

2KEGG_CELL_ADHESION_MOLECULES_CAMS 263 1.980279 0.004938

3KEGG_FRUCTOSE_AND_MANNOSE_METABOLISM 68 1.97929 0.003679

4 KEGG_ALLOGRAFT_REJECTION 30 1.976024 0.003327

5KEGG_STARCH_AND_SUCROSE_METABOLISM 52 1.950593 0.00447

6 KEGG_LYSOSOME 245 1.924518 0.005045

7KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION 160 1.881129 0.006712

8 KEGG_GRAFT_VERSUS_HOST_DISEASE 23 1.862613 0.006288

9 KEGG_OTHER_GLYCAN_DEGRADATION 26 1.845861 0.006572

10 KEGG_BLADDER_CANCER 99 1.835897 0.007127

11KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 96 1.825939 0.007579

12 KEGG_AUTOIMMUNE_THYROID_DISEASE 37 1.822213 0.007031

13 KEGG_ARACHIDONIC_ACID_METABOLISM 62 1.818077 0.006583

14KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM 84 1.790679 0.008669

15KEGG_DORSO_VENTRAL_AXIS_FORMATION 59 1.788125 0.008309

16KEGG_HYPERTROPHIC_CARDIOMYOPATHY_HCM 206 1.772318 0.008852

17 KEGG_DILATED_CARDIOMYOPATHY 230 1.749563 0.010844

18 KEGG_VIBRIO_CHOLERAE_INFECTION 125 1.744738 0.010825

19 KEGG_INSULIN_SIGNALING_PATHWAY 332 1.714327 0.014388

Liu et al. Supplementary Figure S3

Page 4: SHC2416.58319p13.3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34531.73319p13.3cell division cycle 34 GZMM544.03419p13.3granzyme M

Con Zbtb7aΔ/Δ0

100200300400500600700800900

1000

0

1

2

3

4

5

6

7

0

0.2

0.4

0.6

0.8

1

1.2

Mcam Mcam Zbtb7a

Mcam

Hsp90

Zbtb7a

Primary MEF Transformed MEF

Microarray data Rt-PCR

Con Zbtb7aΔ/Δ Con Zbtb7aΔ/Δ

A

B

Con Zbtb7aΔ/Δ Con Zbtb7aΔ/Δ

P=1x10-6P=1x10-5

P=0.01

Re

lativ

e m

RN

A e

xpre

ssio

n

Re

lativ

e m

RN

A e

xpre

ssio

n

Re

lativ

e m

RN

A e

xpre

ssio

n

Liu et al. Supplementary Figure S4

Page 5: SHC2416.58319p13.3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34531.73319p13.3cell division cycle 34 GZMM544.03419p13.3granzyme M

MCAM Prognosis A

B

-0.3

-0.295

-0.29

-0.285

-0.28

-0.275

-0.27

-0.265

-0.26

Primar

y m

elan

oma

Met

asta

sis m

elan

oma

MCAM CNV

1.0

0.8

0.6

0.4

0.2

0.0

0 1000 2000 3000 4000

Su

rviv

al p

rob

ab

ility

Time (Days)

High MCAM expression

Low MCAM expression

n. s.

P=0.005

Re

lativ

e C

NV

va

lue

Liu et al. Supplementary Figure S5

Page 6: SHC2416.58319p13.3 SHC (Src homology 2 domain containing) transforming protein 2 CDC34531.73319p13.3cell division cycle 34 GZMM544.03419p13.3granzyme M

(Human)(Mouse)

Sequence alignment between human and mouse MCAM promoter

A

E

D

FLAG-ZBTB7A

ZBTB7AZBTB7A

b-actin

B

FLAG-ZBTB7A

Con

Con ZBTB7A Con ZBTB7A

P=0.002 P=0.0004

% in

put

% in

put

MCAM promoter primer 2#

MCAM promoter primer 3#

0

0.2

0.4

0.6

0.8

1

1.2

1.4

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Liu et al. Supplementary Figure S6

Conserved ZBTB7A binding sites in human MCAM promoter

0.65

0.7

0.75

0.8

0.85

0.9

0

5

10

15

20

25

Luci

fera

se/R

enill

a pGL3 (basic)

pGL3-MCAM

ZBTB7A --

Luci

fera

se/R

enill

a

ZBTB7A --

C

P=0.0005P=0.00002

P=0.0001