Dooley165548_SuppFig1

A 19 20 20 Rbflox/flox 19 20 Rb∆/∆ 20 Viral-Cre 1 11 1 11 p53flox/flox 1 11 ∆/∆ 1 11 B C D E

F G H I

J L K 100 2.5x107 PFU 1x108 PFU 75

50

25 Percent Survival

0 0 250 500 750 Days post infection Dooley165548_SuppFig2

A Nfib Nfib B Nfib Nfib 5 4 8 14 984T3 3588Liv 3151T1 984LN 7 12 4 3 6 10 5 3 8 2 4 6 2 3 4 1 2 1 1 2 DNA Copy Number Ratio DNA (Tumor/Somatic)

0 0 Copy Number Ratio DNA (Tumor/Somatic) 0 0 70 75 80 85 90 95 70 75 80 85 90 95 70 75 80 85 90 95 70 75 80 85 90 95 4 Position (Mb) Chromosome 4 Position (Mb) Dooley165548_SuppFig3

A B L- Amplification Mycl1 Mycl1 65 7 45 30 984LN 3082T1 25 6 5 25 5 5 4 20 4

o 3 i 15 t 3

a 2

R 10

2 r 1 e 5 b 1

DNA copy number ratio DNA 0 m

u 0 0 ) c N 114 118 122 126 130 114 118 122 126 130 Tumors Mets i

t a y 50 2/15 (13%) 4/13 (31%) p m o o 3151T1 30 3151Liv S / C

r 40 C o 25

A 3

m 1.0x10 N u

T 30 ( D 20

15 3.2x101 20 10 10 1.0x100 5

0 0 -2 114 118 122 126 130 114 118 122 126 130 3.1x10

Chromosome 4 Position (Mb) L-myc expression 9.8x10-4 0.25 0.5 1 2 4 8 16 32 64 128 D Chr. 4 Nfib expression 121 122 123 124 Mb

984LN 3151Liv 3151T1 3151Liv 1.5 3526LN 984T3 3526LN 0.1 3082T1 -0.1 3151T1 3082LN 3588Liv -1.5 3588T1 3588T3 984T2 984T6

Rlf OTTMUSG00000008910 Mycl1 Pabpc4 Rhbdl2 Pou3f1 Mtf1 OTTMUSG00000008911 Trit1 Bmp8a Mycbp Utp11l Yrdc 9530002B09Rik Bmp8b Macf1 Rragc Fhl3 Epha10 Ppt1 Ppie Ndufs5 Sf3a3 Cdca8 Cap1 Hpcal4 Akirin1 Inpp5b Rspo1 Mfsd2 Nt5c1a Heyl Dooley165548_SuppFig4

A

Chromosome 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 X

984LN

3151Liv

3151T1

3151T1 1.5 984T3

3588T1 0.1 3588Liv -0.1

3082LN

3588T3 -1.5

984T2

3082T1

984T6

3526LN

3151Liv

3526LN Dooley165548_SuppFig5

A B Nfib NFIB not not amplified amplified amplified amplified

4 2 11 12 amplified amplified L-myc L-MYC not

not 12 10 5 18 amplified amplified Dooley165548_SuppFig6

A 100 B -

75 Nfib

50 C NEBs (%) + 25 Nfib

0 n = 42 n = 43 neg. mixed CGRP Nfib Dooley165548_SuppFig7

A B C

D Liv E F 100 75

50 T A 25 Percent of Lesions 0 n = 12 n = 25 n = 13 n = 12 n = 638 LN Inv. Dis. Liver

L In situ positive weak negative Dooley165548_SuppFig8

NFIB A 100 90 80 3

2 DNA copy DNA

number ratio 1

0 H82 N417 H446 H889 H196 H524 H2171 H69AR SHP-77 Dooley165548_SuppFig9

A negative 24/68 (35%) weak /moderate strong 11/68 (16%) 33/68 (49%) Dooley165548_SuppFig10

A B ol ol Cont r shRNA2 shRNA1 Cont r shRNA2 shRNA1

NFIB NFIB HSP90

HSP90

C D NCI-H82 30 ol 20 (%) Cont r shRNA1 shRNA2 +

NFIB 10 BrdU

HSP90 0 shRNA1shRNA2 Cont. Uninf. Dooley165548_SuppFig11

A B C L-myc - + - + 20 Nfib - - + + ** Nfib 15 ** Uninf. L-myc Hsp90 10 *

5 L-myc Soft Agar Colonies (#) Soft 0 Hsp90 Uninf.L-myc Nfib L-myc N b L-myc & N b & Nfib D E 6 6 4.0x10 L-myc & Nfib 3.0x10 L-myc & Nfib Nfib Nfib 6 3.0x10 L-myc L-myc 2.0x106 Uninf. Uninf. 2.0x106 Cells (#) Cells (#) 1.0x106 1.0x106

0 0 0 1 2 3 4 0 1 2 3 4 Day Day Dooley165548_SuppFig12

Curated Sets NES Gene Set Description

Korkola_Teratoma 2.13 predicting the teratoma subtype of nonseminomatous male germ cell tumors Browne_Interferon_Responsive_Genes 2.13 Genes up-regulated in primary fibroblasts following treatment with interferon alpha for 6 hours Lastowska_Coamplified_with_MYCN 1.92 Genes co-amplified with MYCN in primary neuro- blastoma tumors Lian_LIPA_Targets_6M -2.65 Genes up-regulated in lungs from 6 month old LIPA knockout mice Markey_RB1_Chronic_LOF_Dn -2.53 Genes down-regulated in MEFs isolated from RB1 knockout mice Yu_MYC_Targets_Dn -1.95 Genes down-regulated in B cell lymphomas expressing an activated form of MYC Dooley165548_SuppFig13

+/+ A p53 p53-/- B L-myc - + - + L-myc - + - + p53+/+ Nfib - - + + Nfib - - + + 25 *** Nfib Nfib 20 Uninf. L-myc 15 *** Hsp90 Hsp90 10 Colonies (#) L-myc L-myc Low Density 5 0 Hsp90 Hsp90 Nfib L-myc & Nfib Uninf. L-myc Nfib L-myc & Nfib C D p53-/- p53+/+ p53-/- 175 12.5 75 ** ** *** *** *** 150 ** 10.0 125 50 Uninf. L-myc 100 7.5 75 5.0 Foci (#) 50 Foci (#) * 25 Colonies (#) Low Density 2.5 25 0 0 0 Nfib L-myc & Nfib Uninf. L-myc Nfib L-myc Uninf. L-myc Nfib L-myc Uninf. L-myc Nfib L-myc & Nfib & Nfib & Nfib E p53-/- 100 *** *** 75

50

Soft Agar Soft 25

Colonies (#) *** 0 Uninf. L-myc Nfib L-myc & Nfib Dooley165548_SuppTable2 Sample DNA Source Total reads Confidently aligned reads

Somatic1 tail 4064293 1694532 Somatic2 tail 5212109 2858180 129Som tail 5430824 3470755 Total Somatic 14707226 8023467 984LN cell line 4514631 3065735 984LN fresh tissue 5909969 3096862 984T6 cell line 5910893 3938360 984T2 fresh tissue 5946141 3880381 984T3 fresh tissue 6336110 3534753 3588T1 fresh tissue 6715350 4414906 3588T3 fresh tissue 6590516 4391195 3588Liv fresh tissue 6359123 4262816 3082T1 cell line 6101749 4261614 3082LN cell line 6312999 4357165 3151T1 fresh tissue 6505090 4081703 3151Liv cell line 6874539 4666647 3526LN cell line 6955500 3993508 3151T1 cell line 6066834 1649405 3151Liv fresh tissue 8522947 5861214 3526LN fresh tissue 7552605 4940323