Visscher D W, Wallis T, Awussah S, Mohamed A, Crissman J D
Department of Pathology, Harper Hospital, Detroit, Michigan 48201, USA.
Genes Chromosomes Cancer. 1997 Jan;18(1):1-7.
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 tumors. None of the benign tissues and neither of the phyllodes tumors demonstrated 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 seven 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 carcinomas 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 MYC copies. The number of MYC copies correlated with cellular DNA content, as determined by using flow cytometry. In peridiploid tumors (DNA index 0.9-1.2; n = 7), the MYC copy numbers/nucleus were 0-2 in five cases and 3-5 in two cases. In contrast, the modal MYC copy numbers/nucleus among the 11 hyperdiploid tumors (DNA index 1.3-1.9) were 0-2 in one 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/nucleus. We conclude that an increased MYC copy number, as detected by using interphase cytogenetics, is extremely frequent in human breast carcinomas. However, in most cases, MYC gene duplication is probably secondary to polysomy of chromosome 8 and/or genomic endoreduplication (i.e., DNA aneuploidy).
我们采用荧光原位杂交（FISH）技术，对24例乳腺癌、7例乳腺良性样本及2例叶状肿瘤的全核印记标本进行MYC基因及8号染色体拷贝数检测。所有良性组织及叶状肿瘤均未显示MYC基因或8号染色体拷贝数增加，拷贝数增加定义为超过10%的细胞核中信号数大于2个。相比之下，24例乳腺癌中有22例显示MYC基因拷贝数增加。细胞核中MYC拷贝数的众数在7例（29%）中为0 - 2个，7例（29%）中为3 - 5个，5例（21%）中为6 - 9个，5例（21%）中大于9个。在22例有MYC基因扩增的乳腺癌中，21例观察到8号染色体拷贝数增加，细胞核中信号数的众数与MYC拷贝数相同（n = 14；64%）或少于MYC拷贝数（n = 8；36%）。通过流式细胞术测定，MYC拷贝数与细胞DNA含量相关。在亚二倍体肿瘤（DNA指数0.9 - 1.2；n = 7）中，5例细胞核中MYC拷贝数为0 - 2个，2例为3 - 5个。相比之下，11例超二倍体肿瘤（DNA指数1.3 - 1.9）中，细胞核中MYC拷贝数的众数1例为0 - 2个，4例为3 - 5个，5例为6 - 9个，1例大于9个。所有3例四倍体/超四倍体乳腺癌细胞核中MYC拷贝数均大于9个。我们得出结论，通过间期细胞遗传学检测发现，MYC基因拷贝数增加在人类乳腺癌中极为常见。然而，在大多数情况下，MYC基因复制可能继发于8号染色体多体性和/或基因组核内复制（即DNA非整倍体）。
