Comprehensive molecular portraits of invasive lobular breast cancer Journal Article


Authors: Ciriello, G.; Gatza, M. L.; Beck, A. H.; Wilkerson, M. D.; Rhie, S. K.; Pastore, A.; Zhang, H.; McLellan, M.; Yau, C.; Kandoth, C.; Bowlby, R.; Shen, H.; Hayat, S.; Fieldhouse, R.; Lester, S. C.; Tse, G. M. K.; Factor, R. E.; Collins, L. C.; Allison, K. H.; Chen, Y. Y.; Jensen, K.; Johnson, N. B.; Oesterreich, S.; Mills, G. B.; Cherniack, A. D.; Robertson, G.; Benz, C.; Sander, C.; Laird, P. W.; Hoadley, K. A.; King, T. A.; TCGA Research Network; Perou, C. M.
Article Title: 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. © 2015 Elsevier Inc.
Journal Title: Cell
Volume: 163
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2015-10-08
Start Page: 506
End Page: 519
Language: English
DOI: 10.1016/j.cell.2015.09.033
PROVIDER: scopus
PMCID: PMC4603750
PUBMED: 26451490
DOI/URL:
Notes: Export Date: 2 November 2015 -- Source: Scopus
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MSK Authors
  1. Tari King
    165 King
  2. Chris Sander
    196 Sander
  3. Sikander Hayat
    5 Hayat
  4. Cyriac Kandoth
    17 Kandoth
  5. Alessandro   Pastore
    22 Pastore