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PMID: 23374354 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Integrative eQTL-based analyses reveal the biology of breast cancer risk loci.

Cell ·Vol. 152 ·No. 3 ·2013-01-31 ·Pages 633-41

Li Q, Seo JH, Stranger B, McKenna A, Pe'er I, Laframboise T, Brown M, Tyekucheva S, Freedman ML

Abstract

Germline determinants of gene expression in tumors are infrequently studied due to the complexity of transcript regulation caused by somatically acquired alterations. We performed expression quantitative trait locus (eQTL)-based analyses using the multi-level information provided in The Cancer Genome Atlas (TCGA). Of the factors we measured, cis-acting eQTLs accounted for 1.2% of the total variation of tumor gene expression, while somatic copy-number alteration and CpG methylation accounted for 7.3% and 3.3%, respectively. eQTL analyses of 15 previously reported breast cancer risk loci resulted in the discovery of three variants that are significantly associated with transcript levels (false discovery rate [FDR] < 0.1). Our trans-based analysis identified an additional three risk loci to act through ESR1, MYC, and KLF4. These findings provide a more comprehensive picture of gene expression determinants in breast cancer as well as insights into the underlying biology of breast cancer risk loci.

MeSH Terms
Breast Neoplasms/genetics Cell Line, Tumor Gene Expression Profiling Genetic Predisposition to Disease Genome-Wide Association Study Humans Kruppel-Like Factor 4 Quantitative Trait Loci
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Li Qiyuan
Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Seo Ji-Heui
Stranger Barbara
McKenna Aaron
Pe'er Itsik
Laframboise Thomas
Brown Myles
Tyekucheva Svitlana
Freedman Matthew L
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2012.12.034
Published
2013-01-31
Pages
633-41
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4165609
Subset
IM
Grants
NCI NIH HHS · R01 CA129435 · United States
NCI NIH HHS · R01 CA131341 · United States
NCI NIH HHS · U19 CA148537 · United States
Corrections
CommentIn
PMID: 23374335
External Links
PubMed source DOI: 10.1016/j.cell.2012.12.034 PMC Full Text View journal details
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