Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer
Creators: name: Gehlenborg, Nils
name: Mills, Gordon B.
name: Ramirez, Nilsa C.
name: Mungall, Andrew J.
name: Zhang, Hailei
name: Schultz, Nikolaus
name: Ding, Li
name: Wang, Zhining
name: Sofia, Heidi J.
name: Felau, Ina
name: Murray, Bradley A.
name: Wiznerowicz, MacIej
name: Brooks, Denise
name: Yang, Liming
name: Shriver, Craig
name: Chin, Lynda
name: Jefferys, Stuart R.
name: Perou, Charles M.
name: Gibson, William J.
name: Holbrook, Andrea
name: Jones, Steven J.M.
name: Shi, Yan
name: Gatza, Michael L.
name: Tarnuzzer, Roy
name: Roach, Jeffrey
name: Gabriel, Stacey B.
name: Shaw, Kenna R.Mills
name: Beroukhim, Rameen
name: Robertson, A. Gordon
name: Hoyle, Alan P.
name: Lolla, Laxmi
name: Holt, Robert A.
name: Olopade, Olufunmilayo
name: Wu, Junyuan
name: Zack, Travis I.
name: Davidsen, Tanja
name: Naresh, Rashi
name: Kim, Jaegil
name: Liu, Wenbin
name: Gastier-Foster, Julie M.
name: Liu, Jia
name: Pastore, Alessandro
name: Wilson, Richard
name: Frazer, Scott
name: Benz, Christopher
name: Huang, Mei
name: Schein, Jacqueline E.
name: Kandoth, Cyriac
name: Rhie, Suhn K.
name: Soloway, Matthew G.
name: Hwang, E. Shelley
name: Boice, Lori
name: Cho, Juok
name: Meyerson, Matthew
name: Benz, Stephen
name: Saksena, Gordon
name: Fieldhouse, Robert
name: Hu, Hai
name: Leraas, Kristen M.
name: Laird, Peter W.
name: King, Tari A.
name: Getz, Gad
name: Ju, Zhenlin
name: Johnson, Nicole B.
name: McAllister, Cynthia
name: Pihl, Todd
name: Marks, Jeffrey
name: Sun, Charlie
name: Wise, Lisa
name: Ling, Shiyun
name: Lichtenberg, Tara M.
name: Barr, Thomas
name: Balasundaram, Miruna
name: Gerken, Mark
name: Weinstein, John N.
name: Lester, Susan C.
name: Weisenberger, Daniel J.
name: Tse, Gary M.K.
name: Zhang, Jiashan
name: Marra, Marco A.
name: Shen, Hui
name: Sander, Chris
name: Chudamani, Sudha
name: Zmuda, Erik
name: Parker, Joel S.
name: Collins, Laura C.
name: Tiezzi, Daniel G.
name: Hutter, Carolyn M.
name: Zenklusen, Jean C.
name: Sougnez, Carrie
name: Lawrence, Michael S.
name: Lu, Yiling
name: Bowlby, Reanne
name: Robertson, Gordon
name: Moore, Richard A.
name: Simons, Janae V.
name: Bootwalla, Moiz S.
name: Meng, Shaowu
name: Cherniack, Andrew D.
name: Shih, Juliann
name: Hoadley, Katherine A.
name: Berrios, Mario
name: Auman, J. Todd
name: Akbani, Rehan
name: Beck, Andrew H.
name: McLellan, Michael
name: Demchok, John A.
name: Maglinte, Dennis T.
name: Schumacher, Steven E.
name: Lai, Phillip H.
name: Bodenheimer, Tom
name: Allison, Kimberly H.
name: Bowen, Jay
name: Yau, Christina
name: Gao, Jian Jiong
name: Ferguson, Martin L.
name: Mose, Lisle E.
name: Sheth, Margi
name: Jensen, Kristin
name: Mardis, Elaine
name: Van Den Berg, David J.
name: Voet, Doug
name: Heiman, David I.
name: Hayes, D. Neil
name: Oesterreich, Steffi
name: Rathmell, W. Kimryn
name: Wilkerson, Matthew D.
name: Lin, Pei
name: Ma, Yussanne
name: Hayat, Sikander
name: Balu, Saianand
name: Noble, Michael S.
name: Shelley, Carl Simon
name: Chen, Yunn Yi
name: Factor, Rachel E.
name: Wu, Ye
name: Wan, Yunhu
name: Ciriello, Giovanni
name: Dennison, Jennifer B.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2015

description: 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.