作者
Michael J Madsen, Stacey Knight, Carol Sweeney, Rachel Factor, Mohamed Salama, Inge J Stijleman, Venkatesh Rajamanickam, Bryan E Welm, Sasi Arunachalam, Brandt Jones, Rakesh Rachamadugu, Kerry Rowe, Melissa H Cessna, Alun Thomas, Lawrence H Kushi, Bette J Caan, Philip S Bernard, Nicola J Camp
发表日期
2018/6/1
期刊
Cancer Epidemiology, Biomarkers & Prevention
卷号
27
期号
6
页码范围
644-652
出版商
American Association for Cancer Research
简介
Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding.
Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis.
Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic …
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