2 DISTINCT AMPLIFIED REGIONS AT 17Q11-Q21 INVOLVED IN HUMAN PRIMARY BREAST-CANCER

Chromosomal segment 17q11-q21 is a commonly amplified region in human breast carcinomas. Several lines of evidence suggest that ERBB2 is the gene responsible for the emergence of this amplicon, but four novel g enes (called MLN 50, MLN 51, MLN 62, and MLN 64) in 17q11-q21 have rec ently been found to be amplified and overexpressed in breast cancer ce ll lines. We investigated 98 primary breast tumors for amplification o f these five loci. Twenty-five tumors (25.5%) showed amplification of at least one of these markers, but most amplifications did not encompa ss all of the tested loci. The genes most frequently amplified were ER BB2 and MLN 64 (22 of 25 amplified cases). MLN 64 was always coamplifi ed with ERBB2, and to a similar level. Amplification of these five gen es always leads to overexpression of their mRNA; we observed no cases of overexpression without amplification in any of these genes. Our res ults suggest that: (a) an independent, amplified region defined by MLN 62 (also called CART1 or TRAF4) is located in 17q11-q12; (b) in addit ion to ERBB2, MLN 64 is a major target for the 17q12-q21 amplicon; and (c) these MLN genes could be of pathogenetic significance in breast c ancer.