Mandahl Nils, Magnusson Linda, Nilsson Jenny, Viklund Björn, Arbajian Elsa, von Steyern Fredrik Vult, Isaksson Anders, Mertens Fredrik
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, SE-221 84 Lund, Sweden.
Array and Analysis Facility, Uppsala University, Uppsala, Sweden.
Mol Cytogenet. 2017 Jun 24;10:25. doi: 10.1186/s13039-017-0325-5. eCollection 2017.
Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes , and from 12q, but often also sequences from other chromosomes.
The present study presents a DDLS with an atypical hypertriploid karyotype without any ring or giant marker chromosomes. SNP array analyses revealed amplification of almost the entire 5p and discontinuous amplicons of 12q including the classical target genes, in particular . In addition, amplicons from 1q, 3q, 7p, 9p, 11q and 20q, covering from 2 to 14 Mb, were present. FISH analyses showed that sequences from 5p and 12q were scattered, separately or together, over more than 10 chromosomes of varying size. At RNA sequencing, significantly elevated expression, compared to myxoid liposarcomas, was seen for and in 5p and of , and in 12q.
The observed pattern of scattered amplification does not show the characteristics of chromothripsis, but is novel and differs from the well known cytogenetic manifestations of amplification, i.e., double minutes, homogeneously staining regions and ring chromosomes. Possible explanations for this unusual distribution of amplified sequences might be the mechanism of alternative lengthening of telomeres that is frequently active in DDLS and events associated with telomere crisis.
非典型脂肪瘤性肿瘤（ALT）、高分化脂肪肉瘤（WDLS）和去分化脂肪肉瘤（DDLS）的细胞遗传学特征为近二倍体核型，除了额外的环状或巨大标记染色体外，没有或仅有少数其他畸变，尽管DDLS往往具有更复杂的重排。相比之下，多形性脂肪肉瘤（PLS）具有高度异常和异质性的核型。环状和巨大标记染色体包含不连续的扩增子，特别是包括来自12q的靶基因、和的多个拷贝，但通常也包含来自其他染色体的序列。
本研究呈现了一例具有非典型超三倍体核型且无任何环状或巨大标记染色体的DDLS。单核苷酸多态性阵列分析显示几乎整个5p扩增以及12q的不连续扩增子，包括经典靶基因，特别是。此外，还存在来自1q、3q、7p、9p、11q和20q的扩增子，覆盖范围从2到14 Mb。荧光原位杂交分析表明，5p和12q的序列分散在10多条大小各异的染色体上，单独或一起分布。在RNA测序中，与黏液样脂肪肉瘤相比，5p中的和以及12q中的、和表达显著升高。
观察到的分散扩增模式不显示染色体碎裂的特征，而是新颖的，并且不同于扩增的众所周知的细胞遗传学表现，即双微体、均匀染色区和环状染色体。扩增序列这种不寻常分布的可能解释可能是端粒替代延长机制，该机制在DDLS中经常活跃，以及与端粒危机相关的事件。
