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Supporting metadata for Therapeutic targeting of BRCA1 and TP53 Mutant Breast Cancer Through Mutant p53 Reactivation

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posted on 2019-04-17, 13:47 authored by Bing Na, Xin Yu, Tracy Withers, John Gilleran, Ming Yao, Tzeh Keong Foo, Chunxian Chen, Dirk Moore, Yong Lin, S. David Kimball, Bing Xia, Shridar Ganesan, Darren R. Carpizo
This data record describes the statistical data supporting the figures in the related publication "Therapeutic targeting of BRCA1 and TP53 Mutant Breast Cancer Through Mutant p53 Reactivation".

Triple negative breast cancer (TNBC) is an aggressive subset of breast cancers, for which a significant portion of patients have have germline or somatic mutations in BRCA1, or epigenetic silencing of BRCA1, which renders them deficient in DNA repair. TNBC is typically treated with chemotherapy.

The related study hypothesizes that restoring wild type p53 function in BRCA1 deficient breast cancer would be therapeutic. It is suggested that inactivation of TP53 is a requirement for tumor progression in the setting of BRCA1 deficiency.

Zinc metallochaperones (ZMCs) are a new class of anti-cancer drugs that reactivate zinc deficient mutant p53 by restoring zinc binding. An aim of the study is preclinical validation of a novel therapeutic approach for BRCA1 deficient breast cancer through reactivation of mutant p53. This includes a novel formulation of ZMC1 and test of its efficacy.

Study design summary

Study includes use of ZMC1 in human breast cancer lines expressing zinc-deficient p53 and use of murine breast cancer models with BRCA1 deficiency to explore survival rates in mice bearing tumors harboring the zinc-deficient Trp53R172H allele but not the Trp53-/-.

A cell survival assay was performed in the context of ZMC1 treatment in human cell lines and mouse models.

Western blot raw data are available within the supplementary information of the related publication. Tumour volume analyses were performed in R statistical package.

All animal experiments were conducted in accordance with the protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Rutgers Robert Wood Johnson Medical School.

Data files and formats

The data supporting the figures of the related manuscript consist of 16 Excel files, 16 Graphpad prism files, 2 jpeg image files and Photoshop image file. All files are accessible through openly available office or image viewer software.

These include cell survival rates in human cell lines and in genetically engineered mouse models treated with ZMC1. Tumor volumes and ZMC sensitivity data are also included.

See the file data_summary_form.xlsx for a more detailed breakdown of the data files supporting each figure.

Data access and terms of use:

Data files are stored in institutional file storage and available on request from Rutgers Cancer Institute of New Jersey:

Darren R. Carpizo, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901. Phone: 732-235-7701. Fax: 732-235-8098. Email: carpizdr@cinj.rutgers.edu

Funding

This work was supported by grants from the National Cancer Institute (K08 CA172676, R01 CA200800) and Breast Cancer Research Foundation (Darren R. Carpizo and Shrida Ganesan).

History

Research Data Support

Research data support provided by Springer Nature.