Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Cell 2015 Oct;163(2):506-19

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2015.09.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603750PMC
October 2015
166 Reads

Publication Analysis

Top Keywords

breast cancer
12
mixed idc/ilc
8
invasive lobular
8
ilc
8
features pten
4
determined three
4
three ilc
4
ilc enriched
4
enriched features
4
pten loss
4
proliferation immune-related
4
increased akt
4
associated increased
4
immune-related signatures
4
signatures determined
4
loss associated
4
foxa1 ilc
4
pten tbx3
4
hallmark identified
4
identified mutations
4

Similar Publications