Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice

Amar H. Mahdi; Yanying Huo; Ying Chen; Pier Selenica; Anchal Sharma; Elise Merritt; Nicola Barnard; Chang Chan; Shridar Ganesan; Jorge S. Reis-Filho; Britta Weigelt; Subhajyoti De; Bing Xia

doi:10.1016/j.gendis.2020.08.012

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Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice

Full-length article | 更新时间：2022-06-24

- Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice
- Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice
- Genes & Diseases 2022年9卷第3期
- 作者机构：
  
  1. Rutgers Cancer Institute of New Jersey, New Brunswick,NJ,USA,08903
  2. Department of Radiation Oncology, Rutgers Robert Wood Johnson Medical School, New Brunswick,NJ,USA,08903
  3. Department of Pathology, Memorial Sloan Kettering Cancer Center,NY,New York,USA,10065
  4. Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick,NJ,USA,08901
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.08.012
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-5-1，
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Amar H. Mahdi, Yanying Huo, Ying Chen, 等. Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice[J]. Genes & Diseases, 2022,9(3).

Amar H. Mahdi, Yanying Huo, Ying Chen, et al. Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice[J]. Genes & Diseases, 2022,9(3).
Amar H. Mahdi, Yanying Huo, Ying Chen, 等. Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice[J]. Genes & Diseases, 2022,9(3). DOI： 10.1016/j.gendis.2020.08.012.

Amar H. Mahdi, Yanying Huo, Ying Chen, et al. Loss of the BRCA1-PALB2 interaction accelerates p53-associated tumor development in mice[J]. Genes & Diseases, 2022,9(3). DOI： 10.1016/j.gendis.2020.08.012.

摘要

Abstract

The BRCA1-PALB2-BRCA2 axis

or the BRCA pathway

plays key roles in genome stability maintenance and suppression of breast and several other cancers. Due to frequent p53 mutations in human

BRCA1

breast cancers and mouse mammary tumors from

Brca1

Brca2

and

Palb2

conditional knockout models

it is often thought that p53 inactivation accelerates BRCA1/2 and PALB2-associated tumorigenesis. Here

we studied tumor development in mice with a mutation in

Palb2

that disengages the PALB2-BRCA1 interaction in different

Trp53

backgrounds. Rather than mammary tumors

Palb2

and

Trp53

compound mutant mice developed

with greatly reduced latencies

lymphomas and sarcomas that are typically associated with germline

Trp53

inactivation. Whole exome sequencing failed to identify any significant differences in genomic features between the same tumor types of

Trp53

single mutant and

Palb2;Trp53

compound mutant mice. These results suggest that loss of the BRCA pathway accelerates p53-associated tumor development

possibly without altering the fundamental tumorigenic processes.

关键词

Keywords

BRCA1BRCA2Osteosarcomap53PALB2Thymic lymphoma

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