Novel mutations in the estrogen receptor messenger RNA in human breast cancers

J Clin Endocrinol Metab. 1996 Apr;81(4):1420-7. doi: 10.1210/jcem.81.4.8636345.


One mechanism that has been suggested to play a role in the progression of human breast cancer from hormone dependence to independence is the expression or altered expression of mutant and/or variant forms of estrogen receptor (ER). Two major types of variant ER messenger (m)RNA have been identified in human breast biopsy samples so far: truncated transcripts and exon deleted transcripts. In this study we provide data indicating the existence of a novel type of abnormal ER mRNA. These transcripts were identified as larger than wild-type ER mRNA RT-PCR products in 9.4% of 212 human breast tumors analyzed. The data suggest nucleotide insertions are present in ER mRNA of some breast tumors. Cloning and sequencing of the larger RT-PCR products showed three different types: a complete duplication of exon 6 occurring in 7.5% of tumors; a complete duplication of both exons 3 and 4 occurring in 1 tumor; and a 69 nucleotide insertion between exons 5 and 6 occurring in 3 tumors. Open reading frame analysis suggested that exon 6 duplicated transcripts encoded a 51.4 kDa ER-like protein truncated just after exon 6 sequences; the exon 3 and 4 duplicated transcript encoded a 83.3 kDa protein containing duplication of ER amino acid residues encoded by exons 3 and 4; the 69 nucleotide insertion was inframe, adding 23 novel amino acid residues between residues 412 and 413 of the normal ER protein to produce a 68.8 kDa protein. It is unknown if these novel ER-like mRNAs are stably translated in vivo. Any resulting protein would be structurally altered, however, possibly resulting in altered function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • DNA Primers
  • DNA Transposable Elements
  • Exons
  • Female
  • Genetic Variation
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • RNA, Messenger / biosynthesis*
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Transcription, Genetic*


  • DNA Primers
  • DNA Transposable Elements
  • RNA, Messenger
  • Receptors, Estrogen

Associated data

  • GENBANK/S82164