FREQUENT ALLELE LOSS ON 9P21-22 DEFINES A SMALLEST COMMON REGION IN THE VICINITY OF THE CDKN2 GENE IN SPORADIC BREAST-CANCER

Genetic studies of chromosome arm 9p have indicated the presence of on e or more tumor suppressor genes involved in genetic susceptibility to various types of human cancers. To define the extent of the specific deletion of 9p21-22 in human breast cancer, we have analyzed loss of h eterozygosity and homozygous deletion of 9p21-22 in 68 paired blood an d tumor samples by using fluorescent multiplex polymerase chain reacti on (PCR). Of these tumors, 43% (29/68), including two ductal carcinoma s in situ (DCIS), showed allele loss at one or more loci analyzed. Hom ozygous deletion for 9p markers was detected in 7/68 (10%) of tumor sa mples. Eleven tumors showed allele loss at all informative loci, and 1 8 tumors showed selective deletion on 9p21-22. Allele deletions in six tumors did not involve microsatellite markers flanking CDKN2. The sma llest common region of deletion could be defined between D9S171 and D9 S126. No significant associations were observed between deletion of 9p 21-22 and any of the histopathological parameters analyzed. However, t he abundance of deletions of this chromosomal region still suggests th at loss and inactivation of putative tumor suppressor gene(s) located on 9p21-22 may be involved in the pathogenesis of breast cancer. (C) 1 996 Wiley-Liss, Inc.