LOSS OF HETEROZYGOSITY ON CHROMOSOME ARM 16Q IN BREAST-CANCER METASTASES

One of the main genetic abnormalities associated with breast carcinoge nesis is the loss of genetic material from chromosome arm 16q. Differe nt groups have identified two regions (16q22.1 and 16q24-ter) that are frequently deleted in primary tumors, suggesting the presence of tumo r suppressor genes in these regions. Little is known about the late st ages of tumor progression in this respect, and we, therefore, analyzed biopsy specimens of breast cancer metastases for deletions in these c ritical regions of 16q. We examined fine needle cytopunctures from 24 metastases, each with lymphocyte DNA, for allelic imbalance on 16q by means of polymerase chain reaction (PCR) with 15 highly polymorphic ma rkers. All the metastatic samples showed deletion of at least one info rmative locus on 16q. The loss of heterozygosity (LOH) pattern often i ndicated the loss of a complete long arm of chromosome 16 (13 cases); nevertheless, in the remaining I I samples, partial LOH patterns were observed. A small region of overlap (SRO2) in 16q22. I was frequently involved, whereas another (SRO I) in 16q24-ter was affected in only tw o cases. A third region of LOH in 16q22.2-q23.2 was found in 6/11 samp les. These results suggest that at least three different regions are i nvolved in allelic imbalance on chromosome arm 16q in breast cancer. L oss of material from the third region could be a major event in the ge nesis of metastases. (C) 1997 Wiley-Liss, Inc.