Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma:: 9p23 neocentromere and 9p23∼p24 amplification including JAK2 and JMJD2C
Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma:: 9p23 neocentromere and 9p23∼p24 amplification including JAK2 and JMJD2C
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DOI：
10.1016/j.cancergencyto.2006.01.004
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发表时间：
2006-06-01
影响因子：
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通讯作者：
Pedeutour, Florence
中科院分区：
文献类型：
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作者：
Italiano, Antoine;Attias, Rita;Pedeutour, Florence
肺肉瘤样癌（LSC）是一种罕见的肺癌，其特征是癌和肉瘤成分的混合物。关于LSC基因组改变的数据几乎不存在。在这里，我们报告的第一个转移性LSC的分子细胞遗传学特征。细胞遗传学和荧光原位杂交（M-FISH）分析表明，近三倍体核型与众多的结构畸变和4至6个小的额外标记染色体含有9号染色体序列。阵列上的比较基因组杂交（阵列CGH）检测到与p24.3相似的9 p23扩增，与q23.3相似的1 q11扩增，与q29相似的3q26.2扩增，与q24.1相似的17q23.2扩增。在同一患者的原发肿瘤和另一个转移瘤中也检测到9 p扩增，表明它是该LSC病例发病机制中的重要因素。互补荧光原位杂交分析表明，小额外染色体为9 p23的等染色体，与p24.3相似。这些等染色体缺乏α-卫星序列，但它们在培养物中传代55次后仍然稳定。如抗着丝粒抗体免疫染色所示，它们含有功能性着丝粒。所谓的近形“新着丝粒”是罕见的，主要是在宪法异常核型描述。该病例是第三次在癌症（即分化良好的脂肪肉瘤和急性髓性白血病）中鉴定新着丝粒的描述，也是第一次在癌症中鉴定新着丝粒。我们的研究结果表明，这种情况下的LSC的9 p23新着丝粒可能是类似的9 p23新着丝粒先前确定在两个宪法的情况下。实体瘤中新着丝粒形成的频率可能确实被低估，并且可能在肿瘤细胞中染色体不稳定性中具有重要意义。(c)2006年爱思唯尔公司All rights reserved.
Sarcomatoid carcinoma of the lung (LSC) is a rare lung cancer characterized by an admixture of carcinoma and sarcoma components. Data concerning the genomic alterations of LSC are almost nonexistent. Here, we report on the first molecular cytogenetic characterization of a metastatic LSC. Cytogenetic and multicolor fluorescence in situ hybridization (M-FISH) analyses showed a near-triploid karyotype with numerous structural aberrations and four to six small supernumerary marker chromosomes containing chromosome 9 sequences. Comparative genomic hybridization on arrays (array CGH) detected an amplification of 9p23 similar to p24.3 and gains of 1q11 similar to q23.3, 3q26.2 similar to q29, and 17q23.2 similar to q24.1. The 9p amplification was also detected in the primary tumor and another metastasis of the same patient, indicating it was a significant element in the pathogenesis of this LSC case. Complementary FISH analysis showed that the small supernumerary chromosomes were isochromosomes for 9p23 similar to p24.3. These isochromosomes were lacking alpha-satellite sequences although they were still stable after 55 passages in culture. As demonstrated by immunostaining with anticentromere antibodies, they contained a functional centromere. So-called analphoid "neocentromeres" are rare and have been mainly described in constitutional abnormal karyotypes. This case is the third description of the identification of neocentromeres in cancer, (i.e. well-differentiated liposarcoma and acute myeloid leukemia), and is the first one in a carcinoma. Our results suggest that the 9p23 neocentromere of this case of LSC might be similar to a 9p23 neocentromere previously identified in two constitutional cases. The frequency of neocentromere formation in solid tumors may indeed be underestimated and may have a significant implication in chromosomal instability in tumor cells. (c) 2006 Elsevier Inc. All rights reserved.