CTCF gene mutations in invasive ductal breast cancer

Breast Cancer Res Treat. 2003 Aug;80(3):347-52. doi: 10.1023/A:1024930404629.

Abstract

The CTCF gene encodes for a transcriptional repressor of the c-myc oncogene and has previously been mapped to one of the smallest regions of overlapping interstitial deletions on chromosome 16q22.1 in invasive breast cancer. This chromosomal region is frequently deleted in both invasive lobular and ductal breast carcinomas. However, no target genes have been identified in invasive ductal breast cancer. We examined CTCF protein expression in 18 invasive ductal breast carcinomas using immunohistochemistry. Additionally, loss of heterozygosity (LOH) at chromosome 16q22.1 was determined and the complete cDNA sequence of CTCF was screened for mutations. Immunohistochemically, 17 tumours showed a moderate to strong nuclear staining for CTCF, one case was completely negative. Sequencing analysis revealed a tumour-specific truncating 14 bp insertion with silencing of the wild type allele in this case. In one further case we found a missense mutation that was shown not to be tumour-specific. Concordant with the antiproliferative effects of the CTCF protein in vivo, CTCF may be involved in tumour initiation or proliferation in individual cases of invasive ductal breast carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • CCCTC-Binding Factor
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology*
  • Chromosomes, Human, Pair 16 / genetics*
  • DNA Mutational Analysis
  • DNA, Complementary / analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Neoplasm Invasiveness*
  • Repressor Proteins*
  • Transcription Factors / genetics*
  • Zinc Fingers

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • DNA, Complementary
  • DNA-Binding Proteins
  • Repressor Proteins
  • Transcription Factors