Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers.

EBAG9, an estrogen-responsive gene located at 8q23 was identified in an effort to clone CpG-binding sites. Its product was later found to be identical to RCAS1, a cancer cell-surface antigen implicated in immune escape. We determined the sequence of the complete cDNA and the genomic structure for EBAG9. EBAG9 gene copy number in 21% (27 of 129) primary breast cancers we examined; EBAG9 mRNA was consistently expressed in cancer cell lines. Detailed physical mapping of the 8q arm, including polymorphic markers for EBAG9 and the CMYC loci, revealed allelic gain of either EBAG9, CMYC, or both, in 45% (58 of 129) of the breast cancers we examined. The EBAG9 gene was increased exclusively in 16 of the 27 tumors showing gain at that locus; the other 11 showed gain of a larger chromosomal region containing both EBAG9 and CMYC. Analysis of subsequent series of 144 primary breast cancers for allelic gain at EBAG9 and CMYC locus showed a similar degree of gain at EBAG9, CMYC, or both. When a total of 273 breast cancers from two series were combined and analyzed for clinicopathological correlation, almost all of the tumors with EBAG9 increased but not those with CMYC. Twenty-eight of 29 were T1/T2 stage carcinomas (<5 cm in diameter), whereas one third (21 of 61) of the tumors in which CMYC was increased but EBAG9 was not, were advanced T3-stage tumors (P = 0.0012). These data suggest that EBAG9 and CMYC gene are independent targets of gain and that overrepresentation of EBAG9 may play a specific role in early stages of breast carcinogenesis.