| Literature DB >> 26451490 |
Giovanni Ciriello1, Michael L Gatza2, Andrew H Beck3, Matthew D Wilkerson4, Suhn K Rhie5, Alessandro Pastore6, Hailei Zhang7, Michael McLellan8, Christina Yau9, Cyriac Kandoth10, Reanne Bowlby11, Hui Shen12, Sikander Hayat6, Robert Fieldhouse6, Susan C Lester3, Gary M K Tse13, Rachel E Factor14, Laura C Collins3, Kimberly H Allison15, Yunn-Yi Chen16, Kristin Jensen17, Nicole B Johnson3, Steffi Oesterreich18, Gordon B Mills19, Andrew D Cherniack7, Gordon Robertson11, Christopher Benz9, Chris Sander6, Peter W Laird12, Katherine A Hoadley20, Tari A King21, Charles M Perou22.
Abstract
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.Entities:
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Year: 2015 PMID： 26451490 PMCID： PMC4603750 DOI： 10.1016/j.cell.2015.09.033
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582