Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Cell. Volume 163 Issue 2: p506–519, 8 October 2015 10.1016/j.cell.2015.09.033

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Data in the GDC

Supplemental Data

• GDC Manifests
  • Open-Access Data - Download Manifest (3 Files)
  • Controlled-Access Data - Download Manifest (4 Files)
• MAF Files
  • Mutations - tcga_brca_washu_unc_merged_042314.dnps_joined.gencode_v19.hugoified.maf.gz
  • MAF MD5 - tcga_brca_washu_unc_merged_042314.dnps_joined.gencode_v19.hugoified.maf.gz.md5
• Data Files
  • Gene Expression Matrix - BRCA817_20140528_log_medcntr.txt
  • Protein Data - TCGA-BRCA-RBN-v2_0_BRCA817freeze.txt
  • Data Freeze Details - BRCA_freeze_3.26.2014_ver06102014.xlsx
  • DESCRIPTION - DESCRIPTION.txt
  • readme - readme

Additional Resources

• Broad Institute FireCloud (link is external) The Broad Institute
• cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
• TCGA Batch Effects (link is external) MD Anderson Cancer Center

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