A point mutation in the human estrogen receptor gene is associated with the expression of an abnormal estrogen receptor mRNA containing a 69 novel nucleotide insertion

A novel ER-like mRNA containing a 69 nucleotideinsertion precisely between exon 5 and 6 sequenceswas previously identified in human breast cancer biopsysamples. Data are presented which suggest that the69 nucleotide sequence is normally present in intron5 of the human estrogen receptor gene. Theregion corresponding to and surrounding this 69 nucleotidesequence was cloned and the nucleotide sequence determined.Cloning and sequencing of the corresponding region ingenomic DNA isolated from a breast tumor expressingthe 69 nucleotide inserted ER mRNA, revealed anA→G point mutation immediately 3′ to the69 nucleotide sequence. This point mutation resulted inthe generation of a consensus splice donor site.A consensus splice acceptor site sequence is normallypresent immediately 5′ to the 69 nucleotide sequence.These data are consistent with the 69 nucleotidesequence being recognized as an exon by thesplicing machinery, and resulting in processing of amature ER mRNA containing the 69 nucleotide insert.