MOLECULAR CYTOGENETIC ANALYSIS OF CONSISTENT ABNORMALITIES AT 8Q12-Q22 IN BREAST-CANCER

Studies using comparative genomic hybridization (CGH) indicate that po rtions of chromosome arm 8q from 8q12 to 8qter are present at an incre ased relative copy number in a broad range of solid tumors. In this st udy we define an similar to 1 Mb wide region that appears to be freque ntly abnormal in copy number or structure in breast cancer cell lines and primary tumors. This was accomplished by fluorescence in situ hybr idization (FISH) with yeast artificial chromosomes (YACs) mapped to 8q 12-q22. Eleven breast cancer cell lines and ten primary tumors were an alyzed. A minimal region of rearrangement was localized to the CEPH-YA C 928F9 in three breast cancer cell lines with unbalanced translocatio n breakpoints mapping in this region. Unbalanced translocations also w ere detected in two primary tumors mapping between CEPH-YAC clones 890 C4 and 936B3, flanking 928F9. An increased copy number in the minimal region was detected in nine cell lines and in multiple primary tumors. This suggests the possibility that a single gene mapping to 928F9 is involved in breast cancer development or progression and may be deregu lated by copy number increases in some tumors and by translocation in others. Four expressed sequence tags were mapped to YAC 928F9 and anal yzed for rearrangements by Southern analysis and for abnormal expressi on by Northern analysis. (C) 1998 Wiley-Liss, Inc.