Differentially amplified in low- and high-grade chromosome 12 sequences osteosarcoma
Differentially amplified in low- and high-grade chromosome 12 sequences osteosarcoma
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DOI：
10.1002/gcc.1219
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发表时间：
2002-02-01
影响因子：
3.7
通讯作者：
Dal Cin, P
中科院分区：
文献类型：
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作者：
Gisselsson, D;Pålsson, E;Dal Cin, P
大多数骨肉瘤是高度侵袭性的恶性肿瘤，其特征是染色体异常的复杂模式。然而，低级别骨旁肿瘤的一个亚组表现出相对简单的畸变模式，主要由携带12号染色体扩增物质的环状染色体支配。为了评估该染色体的序列是否在低级别和高级别骨肉瘤中差异扩增，在24例骨肉瘤中通过间期或中期荧光原位杂交（FISH）评估了12 p中CCND 2、ETV 6、KRAS 2和D12 S85区域以及12 q中MDM 2区域的拷贝数。在所有5例低级别和4例高级别骨肉瘤中均检测到MDM 2扩增，所有病例均显示环状染色体。在1/5的低级别肿瘤和9/19的高级别肿瘤中发现12 p序列的过度表达。对6个高级别肿瘤的中期细胞的多色单拷贝FISH分析表明，额外的12 p物质要么与MDM 2一起出现在环状染色体中，要么由于复杂的结构重排而分散在基因组中。大多数肿瘤（8/10）不包含扩增的评估染色体12位点表现出非二倍体模式的评价与探针的着丝粒α卫星序列。这些发现表明，从12号染色体短臂获得序列可能是侵袭性骨肉瘤发生的一个可能的遗传途径。(C)2002 Wiley-Liss，Inc.
Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors, Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma. (C) 2002 Wiley-Liss, Inc.