Abstract
We have used polymerase chain reaction (PCR) analysis to study the incidence of allelic imbalance at four polymorphic microsatellite markers on chromosome 6q25.1-27, three dinucleotide repeats and one trinucleotide repeat, for microdissected tumour foci from a group of 75 'early' breast carcinomas. The tumours comprised 16 preinvasive cases of ductal carcinoma in situ (DCIS) and 59 mammographically detected early invasive carcinomas. Loss of heterozygosity (LOH) was detected at all four loci and in all types and grade of disease. The frequency of LOH ranged from 23% to 50% depending on the marker studied. The highest frequency of LOH was observed at the D6S186 locus for the cases of DCIS and at the oestrogen receptor locus for the invasive carcinomas. These data suggest that the inactivation of tumour-suppressor genes within this region on chromosome 6q is important for the development of these early lesions.
Highlights
We examined Loss of heterozygosity (LOH) at the more distal region, chromosome 6q25-q27, using four polymorphic microsatellite markers, in a group of 75 'early' lesions comprising 59 mammographically detected invasive carcinomas and 16 preinvasive lesions of ductal carcinoma in situ (DCIS)
A total of 59 early invasive breast tumours and 16 preinvasive lesions of DCIS were screened for LOH with four polymorphic microsatellite markers, mapping to chromosome 6q25
The complex heterogeneity of the disease and the presence of non-tumour cells can mask LOH, all analyses were confirmed using DNA prepared by microdissection from different histological tumour foci within the same tumour section (Figure 1)
Summary
A total of 59 invasive breast carcinomas that were impalpable and detected by mammography were studied. All were from the prevalent round of screening and were detected by the Leicestershire Breast Screening Service. Cases of 15 mm or less in maximum diameter were examined. All had either axillary node sampling or axillary dissection. None of the tumours were from women with either a strong family history of breast cancer or any known inherited predisposition to the development of tumours.
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