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Somatic instability of the DNA sequences encoding the polymorphic polyglutamine tract of the AIB1 gene
  1. P Dai,
  2. L-J C Wong
  1. Department of Oncology, Georgetown University Medical Center, Washington, DC 20057
  1. Correspondence to:
 Dr L-J C Wong
 Department of Oncology, Georgetown University Medical Center, M4000, 3800 Reservoir Rd, NW, Washington, DC 20007;


Background:AIB1 contains a polymorphic polyglutamine tract (poly Q) that is encoded by a trinucleotide CAG repeat. Previously there have been conflicting results regarding the effect of the poly Q tract length on breast cancer. Since poly Q is not encoded by a perfect CAG repeat, the heterozygous polymorphic alleles need to be resolved, to understand the exact DNA sequences encoding poly Q.

Methods: Poly Q encoding sequences of AIB1 from 107 DNA samples, including breast cancer cell lines, sporadic primary breast tumours, and blood samples from BRCA1/BRCA2 mutation carriers and the general population, were resolved by PCR/cloning followed by sequencing of each individual clone.

Results: 25 distinct poly Q encoding sequence patterns were found. More than two distinct sequence patterns were found in a significantly higher proportion of tumours and cell lines than that of the general population, suggesting somatic instability. A significantly higher proportion of cancer cell lines or primary breast tumours than that of the general population contained rare sequence patterns. The proportion of sporadic breast tumours having at least one allele ⩽27 repeats is significantly higher than that in the blood of BRCA1/BRCA2 mutation carrier breast cancer patients or the general population.

Conclusion: The poly Q encoding DNA sequences are somatically unstable in tumour tissues and cell lines. A missense mutation and a very short glutamine repeat in primary tumours suggests that AIB1 activity may be modulated through poly Q, which in turn plays a role in the cotransactivation of gene expressions in breast cancers.

  • AIB1
  • polyglutamine tract in AIB1
  • AIB1 and breast cancer
  • poly Q in AIB1
  • CAG repeats in AIB1
  • ACTR, activator of retinoid and thyroid receptors
  • AIB1, amplified in breast cancer gene 1
  • AR, androgen receptor
  • OR, oestrogen receptor
  • FAM, 6-carboxyfluorescein
  • poly Q, polymorphic polyglutamine tract
  • RAC3, receptor associated co-activator 3
  • TAMRA, 6-carboxytetramethyl rhodamine
  • TRAM-1, thyroid hormone receptor activator molecule 1

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  • This study is supported by DOD Breast Cancer Research Program DAMD17-01-1-0257.