Micci F, Teixeira M R, Bjerkehagen B, Heim S
Department of Cancer Genetics, The Norwegian Radium Hospital, Oslo, Norway.
Cytogenet Genome Res. 2002;97(1-2):13-9. doi: 10.1159/000064038.
Supernumerary ring chromosomes and/or giant marker chromosomes are often seen in soft-tissue tumors of low-grade or borderline malignancy, such as well-differentiated liposarcomas or atypical lipomas. Classic cytogenetic banding techniques have proved insufficient to identify the genomic composition and structure of such rings and markers, but fluorescent in situ hybridization (FISH) studies have shown that they consist mainly of amplified material from chromosome 12, more specifically from bands 12q13-->q15. We have used the new FISH-based screening techniques comparative genomic hybridization (CGH) and multicolor-FISH (M-FISH) in combination with G-banding and analysis by chromosome- and locus-specific fluorescent in situ probes to examine in detail the karyotypic characteristics of 22 lipomatous tumors, most of them classified histologically as well-differentiated liposarcomas, selected because they had been shown to harbor rings and/or marker chromosomes. M-FISH, in contrast to G- banding, was found to be informative with regard to the chromosomal origin of the rings and other markers present, whereas CGH and hybridizations with locus-specific probes helped identify which subchromosomal regions were involved. We found that chromosome bands 12q15-->q21 were always gained, with 12q15-->q21 being amplified (i.e., a green-to-red ratio >2 by CGH) in 14 of 22 tumors. In three tumors, two distinct but close amplicons in 12q could be identified, corresponding to bands 12q13-->q15 and 12q21. The genomic segment 1q21-->q23 was gained in 12 cases, reaching the level of amplification in seven. Bands 6q24 and 7p15, whose pathogenetic involvement in liposarcomas has not been reported previously, were gained in three cases each. In addition, the rings and giant markers often contained interspersed sequences from several other chromosomes that did not give an equally clear impression of being nonrandomly involved.
额外的环状染色体和/或巨大标记染色体常见于低级别或交界性恶性软组织肿瘤中，如高分化脂肪肉瘤或非典型脂肪瘤。经典的细胞遗传学显带技术已证明不足以识别此类环状染色体和标记染色体的基因组组成和结构，但荧光原位杂交（FISH）研究表明，它们主要由12号染色体的扩增物质组成，更具体地说是来自12q13→q15带。我们使用了基于FISH的新筛选技术——比较基因组杂交（CGH）和多色FISH（M-FISH），结合G显带以及通过染色体和位点特异性荧光原位探针进行分析，以详细研究22例脂肪瘤性肿瘤的核型特征，其中大多数在组织学上被分类为高分化脂肪肉瘤，选择这些病例是因为它们已被证明含有环状染色体和/或标记染色体。与G显带不同，发现M-FISH对于存在的环状染色体和其他标记染色体的染色体起源具有信息价值，而CGH和与位点特异性探针的杂交有助于确定哪些亚染色体区域参与其中。我们发现12q15→q21染色体带总是增加，在22例肿瘤中有14例12q15→q21发生扩增（即通过CGH检测绿色与红色比值>2）。在3例肿瘤中，可以识别出12q上两个不同但相邻的扩增子，分别对应于12q13→q15带和12q21带。12例病例中1q21→q23基因组片段增加，7例达到扩增水平。6q24和7p15带此前未报道其在脂肪肉瘤发病机制中的参与情况，各有3例出现增加。此外，环状染色体和巨大标记染色体通常还包含来自其他几条染色体的散布序列，这些序列在非随机参与方面没有同样清晰的表现。
