Frequent loss of heterozygosity at the interferon regulatory factor-1 gene locus in breast cancer

Luciane R. Cavalli, Rebecca B. Riggins, Antai Wang, Robert Clarke, Bassem R. Haddad

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The interferon regulatory factor-1 (IRF1) gene, localized on chromosome 5q31.1, is mutated or rearranged in several cancers including some hematopoietic and gastric cancers. However, whether loss of IRF1 occurs in sporadic breast cancer is unknown. Loss of 5q12-31 is reported in 11% of sporadic breast cancers, and high-resolution array-CGH studies have shown loss at 5q31.1 in 50% of breast cancers with a mutated BRCA1 gene. Functionally, overexpression of IRF1 reduces, and a dominant negative IRF1 construct increases, tumorigenesis of human breast cancer xenografts. Taken together, these observations indicate that the IRF1 gene may play a potentially important role as a breast cancer tumor suppressor gene. In this study, we investigated allelic loss of the IRF1 gene in breast tumor specimens from 52 women with invasive breast cancer using an IRF1 intragenic dinucleotide polymorphic marker. Thirty-seven cases were informative. LOH at the IRF1 locus was detected in 32% of these informative cases (12/37). There was a significant association between IRF1 loss and both older age (P = 0.0167) and earlier stage (Stages 1 and 2) (P = 0.0165). To assess the association of IRF1 mRNA expression with clinical outcomes in breast cancer, we studied data from two published gene expression microarray datasets. In breast cancer patients, low IRF1 mRNA expression is strongly correlated with both risk of recurrence (OR = 3.00; P = 0.003; n = 273 cases) and risk of death (OR = 4.18; P = 0.004; n = 191 cases). Our findings strongly imply a tumor suppressor role for the IRF1 gene in breast cancer.

Original languageAmerican English
Pages (from-to)227-231
Number of pages5
JournalBreast Cancer Research and Treatment
Issue number1
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


  • Breast cancer
  • Disease survival
  • IRF1
  • Interferon regulatory factor-1
  • Tumor suppressor gene

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