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Cell. 2015 Oct 8;163(2):506-19. doi: 10.1016/j.cell.2015.09.033.

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Author information

1
Department of Medical Genetics, University of Lausanne (UNIL), 1011 Lausanne, Switzerland; Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
2
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
3
Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
4
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
5
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.
6
Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
7
The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
8
The Genome Institute, Washington University School of Medicine, MO, 63108, USA.
9
Buck Institute For Research on Aging, Novato, CA, 94945, USA.
10
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
11
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, V5Z4S6, Canada.
12
Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, 49503, USA.
13
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
14
Department of Pathology, School of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
15
Department of Pathology, School of Medicine, Stanford University Medical Center, Stanford University, Stanford, CA, USA.
16
Department of Pathology and Laboratory Medicine, University of California, San Francisco, CA, 94143, USA.
17
Department of Pathology, School of Medicine, Stanford University Medical Center, Stanford University, Stanford, CA, USA; VA Palo Alto Healthcare System, Palo Alto, 94304, CA, USA.
18
Department of Pharmacology and Chemical Biology, Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15232, USA.
19
MD Anderson Cancer Center, The University of Texas, Houston, TX, 77230, USA.
20
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
21
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
22
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address: cperou@med.unc.edu.

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.

PMID:
26451490
PMCID:
PMC4603750
DOI:
10.1016/j.cell.2015.09.033
[Indexed for MEDLINE]
Free PMC Article

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