EVALUATION OF MYC AND CHROMOSOME-8 COPY NUMBER IN BREAST-CARCINOMA BYINTERPHASE CYTOGENETICS

We used fluorescence in situ hybridization (FISH) to determine MYC and chromosome 8 copy number on whole nuclear imprint preparations of 24 breast carcinomas, seven benign breast samples, and two phyllodes tumo rs. None of the benign tissues and neither of the phyllodes tumors dem onstrated an increased copy number for MYC or chromosome 8, which was defined as greater than two signals in >10% of nuclei. In contrast, 22 of 24 carcinomas demonstrated an increased MYC copy number. The modal numbers of MYC copies/nucleus were 0-2 in seven cases (29%), 3-5 in s even cases (29%), 6-9 in five cases (21%), and >9 in five cases (21%). An increased chromosome 8 copy number was observed in 21 of 22 carcin omas with MYC gain, and the modal number of signals/nucleus was either identical to (n = 14; 64%) or less than (n = 8; 36%) the number of MY C copies. The number of MYC copies correlated with cellular DNA conten t as determined by using flow cytometry. In peridiploid tumors (DNA in dex 0.9-1.2; n = 7), the MYC copy numbers/nucleus were 0-2 in five cas es and 3-5 in two cases. In contrast, the modal MYC copy numbers/nucle us among the 11 hyperdiploid tumors (DNA index 1.3-1.9) were 0-2 in on e case, 3-5 in four cases, 6-9 in five cases, and >9 in one case. All three tetraploid/hypertetraploid carcinomas exhibited >9 MYC copies/nu cleus. We conclude that an increased MYC copy number, as detected by u sing interphase cytogenetics, is extremely frequent in human breast ca rcinomas. However, in most cases, MYC gene duplication is probably Sec ondary to polysomy of chromosome 8 and/or genomic endoreduplication (i .e., DNA aneuploidy). (C) 1997 Wiley-Liss, Inc.