Supplementary Materials for

A functional genomic approach to actionable gene fusions for

precision oncology
Jun Li, Hengyu Lu, Patrick Kwok-Shing Ng, Angeliki Pantazi, Carman Ka Man Ip,
Kang Jin Jeong, Bianca Amador, Richard Tran, Yiu Huen Tsang, Lixing Yang, Xingzhi Song,
Turgut Dogruluk, Xiaojia Ren, Angela Hadjipanayis, Christopher A. Bristow, Semin Lee,
Melanie Kucherlapati, Michael Parfenov, Jiabin Tang, Sahil Seth, Harshad S. Mahadeshwar,
Kamalika Mojumdar, Dong Zeng, Jianhua Zhang, Alexei Protopopov, Jonathan G. Seidman,
Chad J. Creighton, Yiling Lu, Nidhi Sahni, Kenna R. Shaw, Funda Meric-Bernstam,
Andrew Futreal, Lynda Chin, Kenneth L. Scott, Raju Kucherlapati*,
Gordon B. Mills*, Han Liang*

*Corresponding author. Email: hliang1@mdanderson.org (H. Liang); millsg@ohsu.edu (G.B.M.);

rkucherlapati@bwh.harvard.edu (R.K.)

Published 9 February 2022, Sci. Adv. 8, eabm2382 (2022)

DOI: 10.1126/sciadv.abm2382

The PDF file includes:

Figs. S1 and S2

Other Supplementary Material for this manuscript includes the following:

Tables S1 and S2
 A B Wilcoxon p = 1.6x10−68
C Wilcoxon p = 4.9x10−113
Wilcoxon p = 4.4x10−3
−7.2x10−1 −7.4x10−1
−4.5x10−1
−4.9x10−1
7.5

10 15 20 25
ALK log2 (RSEM)

30
Frequency

Frequency
5.0

20
2.5

10

5
0.0

0
With Without
ALK fusions ALK fusions −1.0 −0.5 0.0 0.5 −1.0 −0.5 0.0 0.5
Pearson's R Pearson's R

Figure S1. Differential expression analysis between cell lines with and without ALK fusions.

(A) Differential expression analysis between cell lines with and without ALK fusions. (B-C) The distribution of Pearson’s Rs
calculated based on the correlation analysis between the ALK expression of randomly sampled cell lines that do not have ALK
fusions and Crizotinib (B) or NVP−TAE684 (C) drug sensitivity. The orange dashed line indicates the mean of randomly
sampled Pearson’s Rs. The red solid line indicates the Pearson’s R calculated based on correlation analysis between drug sensi-
tivity and ALK expression in cell lines with ALK fusions. One sample Wilcoxon test was performed to calculate the p-value.
 TCGA-D3-A2JC
TAX1BP1 BRAF
CLCN6 TCGA-ER-A19L
RAF1

TCGA-FS-A1ZU
CDC27 BRAF
TCGA-EE-A2MI
TRAK1 RAF1

TCGA-BF-A5EP
ATG7 BRAF

−2 −1 0 1 2

Figure S2. Structural details and exon expression profiles of BRAF (TAX1BP1-BRAF, CDC27-BRAF,
and ATG7-BRAF, left) and RAF1 (CLCN6-RAF1 and TRAK1-RAF1, right) fusions.
Breakpoints are indicated by linked arrows. The mRNA expression (Z-normalized) levels relative to expression levels for
each exon in the respective tumor type are shown. Red and blue colors depict high and low expression levels, respectively.
Exons that code for protein tyrosine kinase domains are marked with red bars.