W. Rathmell
Last active: 8/8/2016

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

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, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, TCGA Research Network, Perou CM
Cell. 2015 163 (2): 506-19

PMID: 26451490 · PMCID: PMC4603750 · DOI:10.1016/j.cell.2015.09.033

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Antigens, CD Breast Neoplasms Cadherins Carcinoma, Ductal, Breast Carcinoma, Lobular Female Hepatocyte Nuclear Factor 3-alpha Humans Models, Molecular Mutation Oligonucleotide Array Sequence Analysis Oncogene Protein v-akt Transcriptome

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