Höglund Mattias, Gisselsson David, Hansen Gunnar B, Säll Torbjörn, Mitelman Felix
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden.
Cancer Res. 2002 May 1;62(9):2675-80.
More than 550 breast adenocarcinomas with clonal chromosomal abnormalities have been reported. Although the aberration pattern is clearly nonrandom, no specific primary or secondary karyotypic abnormality has been identified, and furthermore the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors such as breast cancer is one reason why our understanding of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties, we have used several statistical methods that allow identification and interpretation of karyotypic pathways. These methods were applied on 538 breast cancer karyotypes. The distribution of the number of imbalances/tumor showed a monomodal appearance, indicating that one single mode of karyotypic evolution is operating in this tumor type. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances. The imbalances +1pq, 1q-, 3p-, and +7 appear earlier than expected from random events, and two cytogenetic pathways, one initiated by +1q and followed by 11q- and -22, the other initiated by either 3p- or 1q- and followed by 1p-, 3q-, and 6q-, can be discerned. We also show that +7 and +8q behave independently of the other imbalances and cannot, by simple means, be incorporated in the identified pathway scheme. Although the cytogenetic pathways are well separated at earlier stages, they later converge and include a common set of late imbalances.
已报道了550多例具有克隆性染色体异常的乳腺腺癌。尽管畸变模式明显是非随机的，但尚未发现特定的原发性或继发性核型异常，此外，在疾病进展过程中畸变出现的时间顺序也不清楚。上皮性肿瘤（如乳腺癌）中核型的高度复杂性是我们对细胞遗传学进化顺序理解不清楚的一个原因。为了克服其中一些困难，我们使用了几种统计方法来识别和解释核型途径。这些方法应用于538例乳腺癌核型。不平衡数/肿瘤的分布呈现单峰外观，表明在这种肿瘤类型中存在单一的核型进化模式。我们表明，染色体不平衡的出现存在时间顺序。不平衡+1pq、1q-、3p-和+7的出现早于随机事件预期的时间，可以识别出两条细胞遗传学途径，一条由+1q起始，随后是11q-和-22，另一条由3p-或1q-起始，随后是1p-、3q-和6q-。我们还表明，+7和+8q的行为与其他不平衡无关，无法通过简单方法纳入已识别的途径方案。尽管细胞遗传学途径在早期阶段分得很开，但它们后来会汇聚并包括一组共同的晚期不平衡。
