Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Giovanni Ciriello, Michael L. Gatza, Andrew H. Beck, Matthew D. Wilkerson, Suhn K. Rhie, Alessandro Pastore, Hailei Zhang, Michael McLellan, Christina Yau, Cyriac Kandoth, Reanne Bowlby, Hui Shen, Sikander Hayat, Robert Fieldhouse, Susan C. Lester, Gary M.K. Tse, Rachel E. Factor, Laura C. Collins, Kimberly H. Allison, Yunn Yi ChenKristin Jensen, Nicole B. Johnson, Steffi Oesterreich, Gordon B. Mills, Andrew D. Cherniack, Gordon Robertson, Christopher Benz, Chris Sander, Peter W. Laird, Katherine A. Hoadley, Tari A. King, Rehan Akbani, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Thomas Barr, Stephen Benz, Mario Berrios, Rameen Beroukhim, Tom Bodenheimer, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Denise Brooks, Lynda Chin, Juok Cho, Sudha Chudamani, Tanja Davidsen, John A. Demchok, Jennifer B. Dennison, Li Ding, Ina Felau, Martin L. Ferguson, Scott Frazer, Stacey B. Gabriel, Jian Jiong Gao, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, William J. Gibson, D. Neil Hayes, David I. Heiman, Andrea Holbrook, Robert A. Holt, Alan P. Hoyle, Hai Hu, Mei Huang, Carolyn M. Hutter, E. Shelley Hwang, Stuart R. Jefferys, Steven J.M. Jones, Zhenlin Ju, Jaegil Kim, Phillip H. Lai, Michael S. Lawrence, Kristen M. Leraas, Tara M. Lichtenberg, Pei Lin, Shiyun Ling, Jia Liu, Wenbin Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, Elaine Mardis, Jeffrey Marks, Marco A. Marra, Cynthia McAllister, Shaowu Meng, Matthew Meyerson, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Bradley A. Murray, Rashi Naresh, Michael S. Noble, Olufunmilayo Olopade, Joel S. Parker, Todd Pihl, Gordon Saksena, Steven E. Schumacher, Kenna R.Mills Shaw, Nilsa C. Ramirez, W. Kimryn Rathmell, Jeffrey Roach, A. Gordon Robertson, Jacqueline E. Schein, Nikolaus Schultz, Margi Sheth, Yan Shi, Juliann Shih, Carl Simon Shelley, Craig Shriver, Janae V. Simons, Heidi J. Sofia, Matthew G. Soloway, Carrie Sougnez, Charlie Sun, Roy Tarnuzzer, Daniel G. Tiezzi, David J. Van Den Berg, Doug Voet, Yunhu Wan, Zhining Wang, John N. Weinstein, Daniel J. Weisenberger, Richard Wilson, Lisa Wise, MacIej Wiznerowicz, Junyuan Wu, Ye Wu, Liming Yang, Travis I. Zack, Jean C. Zenklusen, Jiashan Zhang, Erik Zmuda, Charles M. Perou

    Research output: Contribution to journalArticle

    685 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)506-519
    Number of pages14
    JournalCell
    Volume163
    Issue number2
    DOIs
    StatePublished - Oct 8 2015

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    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., ... Perou, C. M. (2015). Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Cell, 163(2), 506-519. https://doi.org/10.1016/j.cell.2015.09.033