Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype
Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype
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DOI：
10.1002/gcc.20445
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发表时间：
2007-06-01
影响因子：
3.7
通讯作者：
Mertens, Fredrik
中科院分区：
文献类型：
--
作者：
Bartuma, Hammurabi;Hallor, Karolin H.;Mertens, Fredrik
常规脂肪瘤的核型变化可分为四类，通常是相互排斥的：染色体带12q13-15的重排，特别是通过易位，导致HMGA2基因的失调，染色体13的物质丢失或重排，多余的环状或巨大的标记染色体，以及染色体带6p21的畸变。在本研究中，272例常规脂肪瘤，其中三分之二为深发性脂肪瘤，对获得性克隆染色体改变进行了核型和临床特征评估。断点和不平衡的非随机分布可以得到证实，83%的病例含有一个或多个先前已知的细胞遗传学标志。与临床特征的相关性显示，与其他染色体畸变的肿瘤相比，具有环状/巨大标记物的脂肪瘤在老年患者中更大，更常位于深部，并且似乎有更大的局部复发倾向。通过位点特异性中期荧光原位杂交（FISH）和RT-PCR进一步评估了HMGA2基因在未表现出任何特征性细胞遗传学变化的病例中可能参与的情况，发现该基因的隐性破坏很少，但全长或截断转录本的表达丰富。通过FISH，我们还可以发现10q22-23的断点不影响MYST4基因，而6p21或8q11-12的断点偶尔也会分别靶向HMGA1或PLAG1基因，在常规脂肪瘤中也是如此。
Conventional lipomas harbor karyotypic changes that could be subdivided into four, usually mutually exclusive, categories: rearrangement, in particular through translocations, of chromosome bands 12q13-15, resulting in deregulation of the HMGA2 gene, loss of material from or rearrangement of chromosome 13, supernumerary ring or giant marker chromosomes, and aberrations of chromosome band 6p21. In the present study, 272 conventional lipomas, two-thirds of them deep-seated, with acquired clonal chromosome changes were assessed with regard to karyotypic and clinical features. A nonrandom distribution of breakpoints and imbalances could be confirmed, with 83% of the cases harboring one or more of the previously known cytogenetic hallmarks. Correlation with clinical features revealed that lipomas with rings/giant markers were larger occurred in older patients, were more often deep-seated, and seemed to have an increased tendency to recur locally, compared with tumors with other chromosome aberrations. The possible involvement of the HMGA2 gene in cases that did not show any of the characteristic cytogenetic changes was further evaluated by locus-specific metaphase fluorescence in situ hybridization (FISH) and RT-PCR, revealing infrequent cryptic disruption of the gene but abundant expression of full length or truncated transcripts. By FISH, we could also show that breakpoints in bands 10q22-23 do not affect the MYST4 gene, whereas breakpoints in 6p21 or 8q11-12 occasionally target the HMGA1 or PLAG1 genes, respectively, also in conventional lipomas.