The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.
Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer.
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Yashar S
YS
Niknafs
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Sumin
S
Han
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Beijing 100850, P. R. China.
Teng
T
Ma
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Breast Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Corey
C
Speers
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Chao
C
Zhang
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Kari
K
Wilder-Romans
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan 48109, USA.
Matthew K
MK
Iyer
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Sethuramasundaram
S
Pitchiaya
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Rohit
R
Malik
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Yasuyuki
Y
Hosono
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
John R
JR
Prensner
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Anton
A
Poliakov
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Udit
U
Singhal
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Lanbo
L
Xiao
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Steven
S
Kregel
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Ronald F
RF
Siebenaler
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Shuang G
SG
Zhao
Department of Computer Science and Centre for Biological Signaling Studies (BIOSS), University of Freiburg, Freiburg 79110, Germany.
Michael
M
Uhl
School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Alexander
A
Gawronski
Breast Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Daniel F
DF
Hayes
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Breast Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Lori J
LJ
Pierce
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Xuhong
X
Cao
Vancouver Prostate Centre, Vancouver, British Columbia, Canada V6H 3Z6.
Colin
C
Collins
Department of Computer Science and Centre for Biological Signaling Studies (BIOSS), University of Freiburg, Freiburg 79110, Germany.
Rolf
R
Backofen
School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.|School of Informatics and Computing, Indiana University, Bloomington, Indiana 47405, USA.|Vancouver Prostate Centre, Vancouver, British Columbia, Canada V6H 3Z6.
Cenk S
CS
Sahinalp
Breast Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
James M
JM
Rae
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Breast Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.|Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Arul M
AM
Chinnaiyan
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.|Breast Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Felix Y
FY
Feng
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen; D013629:Tamoxifen / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D062085:RNA, Long Noncoding; D011960:Receptors, Estrogen; C000628098:long noncoding RNA DSCAM-AS1, human; D013629:Tamoxifen
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