American Association for Cancer Research
crc-23-0044_fig4.png (1.78 MB)

FIGURE 4 from Proteogenomic Approaches for the Identification of NF1/Neurofibromin-depleted Estrogen Receptor–positive Breast Cancers for Targeted Treatment

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posted on 2023-07-26, 14:20 authored by Beom-Jun Kim, Ze-Yi Zheng, Jonathan T. Lei, Matthew V. Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, María del Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella B. Hanker, Nada Mohamed, Susan G. Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew J. Ellis, Eric C. Chang

Establish an IHC assay to detect NF1 protein in FFPE tumor samples. A, IHC was performed on a set of cell lines with varying degrees of NF1 (left). Protein lysates from indicated cell lines were also analyzed by immunoblot as shown on the right. B, IHC was performed to analyze a panel of ER+ PDOs with known NF1 status as determined by DNA sequencing. C, IHC was performed on one of the TMAs from the TMA Breast Cancer Continuum set, in which each TMA contains longitudinal samples from the same patient progressing from DCIS (D) to primary breast cancer (P). Kidney (K) was the normal tissue control on the TMA. Scale bar = 50 μm.


HHS | National Institutes of Health (NIH)

U.S. Department of Defense (DOD)

Cancer Prevention and Research Institute of Texas (CPRIT)

Breast Cancer Research Foundation (BCRF)



A major challenge for targeting the consequence of tumor suppressor disruption is the accurate assessment of protein functional inactivation. NF1 can repress both RAS and ER signaling, and a ComboMATCH trial is underway to treat the patients with binimetinib and fulvestrant. Herein we report a MS-verified NF1 IHC assay that can determine a threshold for NF1 loss to predict treatment response. These approaches may be used to identify and expand the eligible patient population.