TY - JOUR
T1 - Pan-Cancer Analysis Reveals Recurrent BCAR4 Gene Fusions across Solid Tumors
AU - Nickless, Andrew
AU - Zhang, Jin
AU - Othoum, Ghofran
AU - Webster, Jace
AU - Inkman, Matthew J.
AU - Coonrod, Emily
AU - Fontes, Sherron
AU - Rozycki, Emily B.
AU - Maher, Christopher A.
AU - White, Nicole M.
N1 - Funding Information:
C.A. Maher received funding from The Alvin J. Siteman Cancer Center Siteman Investment Program through The Foundation for Barnes-Jewish Hospital Cancer Frontier Fund (grant no. GR0012692) and Barnard Trust (grant no. GR0008791), and The Emerson Collective (grant no. GR0017807). We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital (St. Louis, MO), for the use of the Siteman Flow Cytometry. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant (grant no. P30 CA091842).
Publisher Copyright:
©2022 The Authors; Published by the American Association for Cancer Research.
PY - 2022/10
Y1 - 2022/10
N2 - Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner–with differing upstream regions across a patient cohort–suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation.
AB - Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner–with differing upstream regions across a patient cohort–suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation.
UR - http://www.scopus.com/inward/record.url?scp=85139571598&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-21-0775
DO - 10.1158/1541-7786.MCR-21-0775
M3 - Article
C2 - 35852383
AN - SCOPUS:85139571598
SN - 1541-7786
VL - 20
SP - 1481
EP - 1488
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 10
ER -