Nature - USA (2019-07-18)

Letter reSeArCH

rho=0.440

2

3

4

5

6

−6 −4 −2 02

RP11-356O9.1 log(FPKM)

FOXA1 log(FPKM)

rho=0.676

0

1

2

3

4

−4 −2 02

RP11-356O9.1 log(FPKM)

TTC6 log(FPKM)

FOXA1-positive

stomachprostate

bladderlive r

gall_bladderbreast

salivary_glandoral

colonlung

intestinevagina

bone_marrfallopian_tubeow

pituitarytestis

pancreasskin

endometriesophagusum

adrenalother

blood_vesselcervix

thyroidovary

uterusnerve

adiposeblood

kidneyheart

spleenbrain

lymph_nodemuscle

SSTR1

CLEC14A

CTD−2058B24.2CTD−2058B24.3RP11−259K15.2

NKX2−8

RP11−964E11.2

PAX9TTC6

RP11−356O9.2

FOXA1

RP11−356O9.1

PTCSC3

LINC00609

SFTA

3

NKX2−1

NKX2−1−AS1

MBIP

SLC25A21

SLC25A21−AS1

MIPOL1

Z−score

−4

−2

0

2

4

FOXA1-negative

FOXMIND−SKIL

0

50

100

150

200

0200 400

samples (TCGA)

SKIL (FPKM)

FOXA1−HOXA1

0

10

20

30

0200 400

samples (TCGA)

HOXA1 (FPKM)

0

100

200

300

400

0300 600900

samples (TCGA+mCRPC)

ETV1 (FPKM)

FOXMIND−ETV1

FOXA1−CCNA1

0

10

20

30

0200 400

samples (mCRPC)

CCNA1 (FPKM)

FOXMIND−ASXL1

10

20

0200 400

samples (TCGA)

ASXL1 (FPKM)

FOXA1−WNT1

0

50

100

0200 400

samples (mCRPC)

WNT1 (FPKM)

Hi-jacking

translocations

Swapping

translocations

LNCaP

MDA-PCa-2b

LAPC4

DU145

RWPE1

PNT2

H1299

(lung)

FOXA1-positive

FOXA1-negative

ATAC-Seq signal tracks (peaks mark open chromatin)

CRISPR

sgRNA pairs: sgMIPOL1-UTR

sgFOXMIND_1

sgFOXMIND_2

sgFOXMIND_3

sgCTRL

FOXMIND

MIPOL1 FOXA1 TTC6

MIPOL1-UTR

FOXMIND-FOXA1 locus

Translocations

Duplications

37.4MB 37.45MB 37.5MB 37.55MB 37.6MB 37.65MB 37.7MB

chr14 q13.2−q21.1

focal−gain (WXS)

tandem−duplication (RNA)

37.3MB 37.4MB 37.5MB 37.6MB 37.7MB 37.8MB37.9MB

FOXA1

regulatory

FOXA1 domain

TD

Low

Mid

High

Copy

Gain

Low

Mid

High

Read

Support

a

b c d

ef

g

h

HMECs Cells - Primary mammary epithelium T47D Cells - ER+/FOXA1+ breast cancer

FOXA1 TD

PAX9 TD

HUVEC cells - Umbilical vein endothelium

MIPOL1

PAX9 FOXA1

MIPOL1 TTC6

PAX9 FOXA1

TTC6 MIPOL1

PAX9 FOXA1

TTC6

TDs

DHSs

TDs

DHSs

TDs

DHSs

BActin HPR

T1

Tubulin FOX

A^1 TTC6

MIP

OL1

Housekeeping control genes FOXA1-TD genes

sgCTRL

sgMIPOL1-UTR

sgFOXMIND_ 1

sgFOXMIND_ 2 sgFOXMIND_^3

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Relative expression

p<0.0001

p<0.01

p<0.0001

>40

<0

>26

<0

>60

<0

Extended Data Fig. 9 | See next page for caption.