Somatic change in the estrogen receptor gene associated with altered expression of the progesterone receptor

Using a fragment of the estrogen receptor (ER) cDNA as a probe, Southern blots of HindIII-digested genomic DNA, from breast tumours and non-cancerous tissue, revealed a 1.6 kb hybridizing fragment (1.6KbHF) in 3 out of 30 tumours, and in 31 out of 80 mastectomy samples (16 sectors from each of 5 patients), which was significantly correlated with the absence of progesterone receptor. In 4 of the patients, sectors which showed the 1.6KbHF co-existed in the same breast with sectors which did not. Neither the use of higher concentrations of the restriction enzyme, not high salt extraction of DNA changed the abundance of the 1.6KbHF relative to other bands. Similar studies on EcoRI digests of the same DNA samples failed to show any variants. As a further control, hybridization of the same Southern blots of HindIII-digested DNA, with a cytochrome P450IIA3 cDNA, also failed to show variants in these samples. It is concluded that the presence of the 1.6KbHF represents a somatic change in the nucleus of these samples which may have functional importance.