Program Information
Identification of Associations Between Radiologist-Annotated Imaging Features and Genomic Alterations in Breast Invasive Carcinoma, a TCGA Phenotype Research Group Study
A Rao1*, J Net2 , K Brandt3 , E Huang4 , J Freymann5 , E Burnside6 , J Kirby7 , E Morris8 , E Bonaccio9 , M Giger10 , C Jaffe11 , M Ganott12 , E Sutton13 , H Le-Petross14 , M Zuley15 , B Dogan16 , G Whitman17 , (1) ,,,(2) University of Miami, Miami, Florida, (3) Mayo Clinic, Rochester, Minnesota, (4) National Cancer Institute, NIH, Bethesda, Maryland, (5) Leidos Biomedical Research Inc., Frederick, Maryland, (6) University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, (7) Leidos Biomedical Research Inc., Frederick, Maryland, (8) Memorial Sloan Kettering Cancer Center, New York, New York, (9) Roswell Park Cancer Institute, Buffalo, New York, (10) Univ Chicago, Chicago, IL, (11) Boston University School of Medicine, Boston, MA, (12) University of Pittsburgh Medical Center - Magee Womens Hospital, Pittsburgh, Pennsylvania, (13) Memorial Sloan Kettering Cancer Center, New York, New York, (14) MD Anderson Cancer Center, Houston, Texas, (15) University of Pittsburgh Medical Center - Magee Womens Hospital, Pittsburgh, Pennsylvania, (16) UT MDACC, Houston, TX, (17) UTMDACC, Houston, TX
Presentations
TU-CD-BRB-7 (Tuesday, July 14, 2015) 10:15 AM - 12:15 PM Room: Ballroom B
Purpose:To determine associations between radiologist-annotated MRI features and genomic measurements in breast invasive carcinoma (BRCA) from the Cancer Genome Atlas (TCGA).
Methods:98 TCGA patients with BRCA were assessed by a panel of radiologists (TCGA Breast Phenotype Research Group) based on a variety of mass and non-mass features according to the Breast Imaging Reporting and Data System (BI-RADS). Batch corrected gene expression data was obtained from the TCGA Data Portal. The Kruskal-Wallis test was used to assess correlations between categorical image features and tumor-derived genomic features (such as gene pathway activity, copy number and mutation characteristics). Image-derived features were also correlated with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) status. Multiple hypothesis correction was done using Benjamini-Hochberg FDR. Associations at an FDR of 0.1 were selected for interpretation.
Results:ER status was associated with rim enhancement and peritumoral edema. PR status was associated with internal enhancement. Several components of the PI3K/Akt pathway were associated with rim enhancement as well as heterogeneity. In addition, several components of cell cycle regulation and cell division were associated with imaging characteristics.
TP53 and GATA3 mutations were associated with lesion size. MRI features associated with TP53 mutation status were rim enhancement and peritumoral edema. Rim enhancement was associated with activity of RB1, PIK3R1, MAP3K1, AKT1,PI3K, and PIK3CA. Margin status was associated with HIF1A/ARNT, Ras/ GTP/PI3K, KRAS, and GADD45A. Axillary lymphadenopathy was associated with RB1 and BCL2L1. Peritumoral edema was associated with Aurora A/GADD45A, BCL2L1, CCNE1, and FOXA1. Heterogeneous internal nonmass enhancement was associated with EGFR, PI3K, AKT1, HF/MET, and EGFR/Erbb4/neuregulin 1. Diffuse nonmass enhancement was associated with HGF/MET/MUC20/SHIP, and HGF/MET/RANBP9. Linear nonmass enhancement was associated with PIK3R1 and AKT activity.
Conclusion:MRI-genomic association analysis revealed that several BRCA-associated gene features were associated with radiologist-annotated image features.
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