Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

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.

journal_name

Cell

journal_title

Cell

authors

Ciriello G,Gatza ML,Beck AH,Wilkerson MD,Rhie SK,Pastore A,Zhang H,McLellan M,Yau C,Kandoth C,Bowlby R,Shen H,Hayat S,Fieldhouse R,Lester SC,Tse GM,Factor RE,Collins LC,Allison KH,Chen YY,Jensen K,Johnson NB,O

doi

10.1016/j.cell.2015.09.033

subject

Has Abstract

pub_date

2015-10-08 00:00:00

pages

506-19

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(15)01195-2

journal_volume

163

pub_type

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