Gisselsson D, Höglund M, Mertens F, Mitelman F, Mandahl N
Department of Clinical Genetics, Lund University Hospital, Sweden.
Genes Chromosomes Cancer. 1998 Nov;23(3):203-12. doi: 10.1002/(sici)1098-2264(199811)23:3<203::aid-gcc1>3.0.co;2-5.
The chromosomal organization of amplified chromosome 12 sequences was studied with fluorescence in situ hybridization in six mesenchymal tumors: two osteosarcomas, one lipoma, two liposarcomas, and one fibrosarcoma. All except the fibrosarcoma contained ring and/or giant marker chromosomes. Amplification of chromosome 12 sequences, demonstrated with whole-chromosome paint in all cases, was confined to ring and giant marker chromosomes in four tumors. In one of the osteosarcomas and in the fibrosarcoma, amplified sequences were added to chromosome 12 and to chromosomes 10, 12, 18, and the Y chromosome, respectively. Hybridizations with single-copy probes demonstrated considerable inter- and intracellular variation in the arrangement of chromosome 12 sequences in ring and marker chromosomes. Amplification of 12q13-15 sequences, predominantly from the HMGIC-MDM2 region, was detected in all cases, but the two osteosarcomas also contained amplification of 12p material. This finding, combined with results from previous studies, indicates that 12p amplification is a feature distinguishing osteosarcomas from adipose tissue tumors. A novel finding was the presence of positive signals for chromosome 12 alpha-satellite sequences in ring and marker chromosomes in four cases. Rod chromosomes carrying amplified material, in particular those that were relatively stable, frequently exhibited chromosome 12 negative terminal segments; two of these, present in two separate cases, were shown by C-banding to contain constitutive heterochromatin. The significant intercellular heterogeneity in the number and structure of rings and giant markers in a subset of mesenchymal tumors could be explained by continuous recombination through breakage-fusion-bridge cycles. If so, this process will continue until broken ends become stabilized, for example by acquisition of telomeric segments from other chromosomes.
利用荧光原位杂交技术，对六种间叶组织肿瘤（两例骨肉瘤、一例脂肪瘤、两例脂肪肉瘤和一例纤维肉瘤）中扩增的12号染色体序列的染色体组织进行了研究。除纤维肉瘤外，所有肿瘤均含有环状和/或巨大标记染色体。在所有病例中，用全染色体涂染法证实12号染色体序列的扩增，在四个肿瘤中局限于环状和巨大标记染色体。在其中一例骨肉瘤和纤维肉瘤中，扩增序列分别添加到12号染色体以及10号、12号、18号和Y染色体上。用单拷贝探针进行杂交显示，环状和标记染色体中12号染色体序列的排列在细胞间和细胞内存在相当大的差异。在所有病例中均检测到12q13 - 15序列的扩增，主要来自HMGIC - MDM2区域，但两例骨肉瘤还含有12p物质的扩增。这一发现与先前研究结果相结合，表明12p扩增是骨肉瘤区别于脂肪组织肿瘤的一个特征。一个新发现是，在四例病例的环状和标记染色体中存在12号染色体α卫星序列的阳性信号。携带扩增物质的棒状染色体，尤其是那些相对稳定的，经常表现出12号染色体的负性末端片段；在两个不同病例中出现的其中两个，经C带显示含有组成型异染色质。间叶组织肿瘤亚组中环状和巨大标记物在数量和结构上的显著细胞间异质性，可以通过断裂 - 融合 - 桥循环的连续重组来解释。如果是这样，这个过程将持续进行，直到断裂末端变得稳定，例如通过从其他染色体获得端粒片段。
