PDF(Pubmed)
Abstract：
Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.
摘要：
高分化脂肪肉瘤（WDLS）在多余的环或巨型标记染色体中显示12号染色体（Chr12）上的基因扩增。这些结构已被认为是通过染色体形成的，其次是环化和断裂-融合桥（BFB）循环。为了检验这个假设，我们比较了杆状染色体中WDLSs与Chr12的扩增，以及带有环的WDLSs。两种类型的扩增子共享相同的结构变体（SV）谱，Chr12中的SV频率高于共扩增段，具有融合共扩增染色体的端粒末端的SV，缺乏穿插删除。结合在具有环状染色体的肿瘤中发现具有瞬时杆状结构的细胞，这表明一个逐步的过程，从获得Chr12材料开始，在重塑后，这不符合经典的嗜铬细胞，与其他染色体形成双中心结构。取决于是否以及何时捕获其他染色体的端粒，12q序列的环化或线性增益将占主导地位。
