Altered expression of telomere-associated genes in leukocytes among BRCA1 and BRCA2 carriers

Hiromi Tanaka, Elizabeth A. Phipps, Ting Wei, Xi Wu, Chirayu Goswami, Yunlong Liu, George W. Sledge, Lida Mina, Brittney Shea Herbert

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Telomere dysfunction resulting from telomere shortening and deregulation of shelterin components has been linked to the pathogenesis of age-related disorders, including cancer. Recent evidence suggests that BRCA1/2 (BRCA1 and BRCA2) tumor suppressor gene products play an important role in telomere maintenance. Although telomere shortening has been reported in BRCA1/2 carriers, the direct effects of BRCA1/2 haploinsufficiency on telomere maintenance and predisposition to cancer development are not completely understood. In this study, we assessed the telomere-associated and telomere-proximal gene expression profiles in peripheral blood leukocytes from patients with a BRCA1 or BRCA2 mutation, compared to samples from sporadic and familial breast cancer individuals. We found that 25 genes, including TINF2 gene (a negative regulator of telomere length), were significantly differentially expressed in BRCA1 carriers. Leukocyte telomere length analysis revealed that BRCA1/2 carriers had relatively shorter telomeres than healthy controls. Further, affected BRCA1/2 carriers were well differentiated from unaffected BRCA1/2 carriers by the expression of telomere-proximal genes. Our results link BRCA1/2 haploinsufficiency to changes in telomere length, telomere-associated as well as telomere-proximal gene expression. Thus, this work supports the effect of BRCA1/2 haploinsufficiency in the biology underlying telomere dysfunction in cancer development. Future studies evaluating these findings will require a large study population.

Original languageEnglish (US)
Pages (from-to)567-575
Number of pages9
JournalMolecular Carcinogenesis
Volume57
Issue number4
DOIs
StatePublished - Apr 2018

Keywords

  • BRCA1/2
  • breast cancer
  • gene expression
  • haploinsufficiency
  • telomere length

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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