Article https://doi.org/10.

1038/s41467-023-39160-7

a Driver lncRNA oncoplot

Percentage of
samples with
59569
mutations per
Ratio of exonic / Number of Number of candidate Number of
intronic mutation exonic mutations 629 (24.38%) of 2580 samples samples with
rates mutations per sample mutations per
4.92 0 488 0 0 candidate 291
0
NEAT1 11%
MALAT1 6%
LINC00662 4%
LOHAN2 3%
RP11−442N1.2 2%
RP11−575I8.1 2%
HOXC−AS3 2%
SNHG3 1%
LINC00589 1%
RPPH1 1%
RP11−455B3.1 1%
LOLI1 1%
LOHAN1 1%
RP11−10C24.3 1%
RNU12 0%
RP11−669M16.1 0%
RP1−290I10.3 0%

Mutation type
C>T T>A
C>G T>C
C>A T>G

Cohort
Skin−Melanoma Lymph−BNHL Bladder−TCC Breast−AdenoCa CNS−GBM Lung−SCC Cervix−AdenoCA Breast−LobularCa
ColoRect−AdenoCA Lung−AdenoCA Lymph−NOS Prost−AdenoCA Ovary−AdenoCA Panc−Endocrine Bone−Osteosarc Bone−Leiomyo
Stomach−AdenoCA Head−SCC Uterus−AdenoCA Kidney−RCC Kidney−ChRCC CNS−Oligo Cervix−SCC
Liver−HCC Panc−AdenoCA Thy−AdenoCA Eso−AdenoCa CNS−Medullo Biliary−AdenoCA Lymph−CLL

b LncRNA candidates across all cohorts c Driver lncRNA overlap

Known Novel
6 Pancancer 220 488 27 73 17 59

2 Head−SCC 8 5
Ratio exonic /
3 Prost−AdenoCA 9 7 3 intronic
mutation rate PCAWG HMF
1 Skin−Melanoma 57 P = 5e-10
100
candidates candidates
3 Lymph−BNHL 128 4 3
50
3 Liver−HCC 89 16 6
8 1 34
1 Ovary−AdenoCA 7
LOLI1

1 Panc−AdenoCA 7 Number of experimental 5

exonic mutations validation
1 Bone−Leiomyo 6
P = 2e-06 3 3 P = 0.004
LOLI1

LOHAN1
LOHAN2

RP11−455B3.1

RP11−669M16.1
LINC00662

RP1−290I10.3

RP11−575I8.1
RP11−10C24.3

RP11−442N1.2
HOXC−AS3

RPPH1
NEAT1
LINC00589

MALAT1

SNHG3
RNU12

oncogene
397
tumour supp. NEAT1
both MALAT1
unknown SNHG3 Known cancer lncRNAs
RNU12 (CLC2)
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 RPPH1
2

d Driver lncRNA genomic features Cand Non-Cand e Driver lncRNA clinical features
PhastCons GTEX expression Exonic repetitive Early replication
adj P-value = 0.05

1.000 1.000 100

PhastCons score

Wavelet-smoothed

1e+02
signal values
Percentage

0.100 0.100
30
M●
TPM

1e+00
RPK
0.010 0.010
log2 ratio of means

G
Cand vs NonCand

10
0.001 1e−02 0.001
6
P CAW
P = 9e−9 P < 2e−16 P = 0.38 P = 1e−04 4 GC
Ratio of means = 1.735 Ratio of means = 28.62 Ratio of means = 0.813 Ratio of means = 1.097 st C
c l ose value e
ce t
o
al P
-
valu Mb
2 tan surviv rug P- per
LncBase mirRNA per Mb Distance to protein-coding Exonic content Exonic length
Dis N Ps
miRNA bindings per Mb

D ● S
70 1e+05 ● TCGA MAP
1e+05 1e+05 0 ● ● Lnc
Nucleotides
Nucleotids

50 1e+04
0 1 2 3
CG %

1e+03 1e+03
1e+03 −log10 adj P−value
30
1e+01 1e+01
1e+02
P = 0.002 P = 0.67 P = 0.66 P = 6e−05
Ratio of means = 34.826 Ratio of means = 1.644 Ratio of means = 0.993 Ratio of means = 3.091

ENSG00000241219 (RP11-572M11.1), herein named LOLI1 (LncRNA tissues (Supplementary Fig. S4b). We could detect LOLI1 in two HCC
Oncogene in Liver cancer 1) displayed elevated mutation rates in cell lines, HuH7 and SNU-475 (Fig. 4f and Supplementary Fig. S4d). To
Hepatocellular Carcinoma (HCC) tumours (Figs. 3b and 4d) and was perturb LOLI1 expression, we designed two different antisense oligo-
detected as driver in both the PCAWG and HFM datasets (Fig. 3c). We nucleotides (ASOs) that reduced steady-state levels by >50% in both
could not find any studies on this lncRNA in prior scientific literature. cell lines (Fig. 4e, f and Supplementary Fig. S4d). We evaluated the role
According to the latest GENCODE version 38, its single-annotated of LOLI1 in HCC cell proliferation, by measuring changes in growth
isoform comprises three exons, and displays low expression in normal rates following ASO transfection. The significant decrease in growth

Nature Communications | (2023)14:3342 5