ALLELIC IMBALANCE STUDY OF 16Q IN HUMAN PRIMARY BREAST CARCINOMAS USING MICROSATELLITE MARKERS

The high incidence of allelic imbalance on the long arm of chromosome 16 in breast cancer suggests its involvement in the development and pr ogression of the tumor. Several loss of heterozygosity (LOH) studies h ave led to the assignment of commonly deleted regions on 16q where tum or suppressor genes may be located. The most recurrent LOH regions hav e been 16q22.1 and 16q22.4-qter. The aim of this study was to gain fur ther insight into the occurrence of one or multiple ''smallest regions of overlap'' on 16q in a new series of breast carcinomas. Hence, a de tailed allelic imbalance map was constructed for 46 sporadic breast ca rcinomas, using 11 polymorphic microsatellite markers located on chrom osome 16. Allelic imbalance of one or more markers on 16q was shown by 30 of the 46 tumors (65%). Among these 30 carcinomas, LOH on the long arm of chromosome 16 was detected at all informative loci in 19 (41%) ; 13 of them showed allelic imbalance on the long but not on the short arm, with the occurrence of variable ''breakpoints'' in the pericentr omeric region. The partial allelic imbalance in 11 tumors involved eit her the 16q22.1-qter LOH region or interstitial LOH regions. A commonl y deleted region was found between D16S421 and D16S289 on 16q22.1 in 2 9 of the 30 tumors. The present data argue in favor of an important in volvement of a tumor suppressor gene mapping to 16q22.1 in the genesis or progression of breast cancer. (C) 1995 Wiley-Liss, Inc.