The frequency and mechanism of loss of heterozygosity on chromosome 11q in breast cancer.
Tomlinson IP., Nicolai H., Solomon E., Bodmer WF.
Loss of heterozygosity (LOH, allele loss) occurs frequently on the long arm of chromosome 11 in breast cancer. Seventy-one paired tumour/normal DNA samples from breast cancer patients under 50 years old were studied for allele loss at four microsatellite loci on 11q: D11S29 (11q23.3), NCAM (11q22-q23), D11S968 (11qtel), and D11S1313 (11qcen). The maximum frequency of LOH (approximately 35 per cent) was found at the D11S29 and NCAM loci. This result is consistent with previous studies and the frequency of allele loss is moderate to high compared with the usual baseline of 0-20 per cent. In most of the cases studied, LOH on chromosome 11q could be accounted for by one of two mechanisms. Either chromosomal non-disjunction had occurred, or sequences stretching from the telomere at least as far as NCAM had undergone deletion or mitotic recombination. These results suggest that a putative tumour suppressor gene is most likely to exist near 11q22-q23. There was a very low frequency of microsatellite instability in the tumours. An association was found between lack of progesterone receptor (PgR) expression and LOH at NCAM, suggesting that deletion of sequences on 11q may prevent high levels of PgR expression in some cases.