The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.

隆突性皮肤皮肤肉瘤瘤家族（DPFT）包括与异常PDGFBR信号传导相关的皮肤软组织肿瘤，通常通过COL1A1-PDGFB融合产生。本研究的目的是获得对该融合的染色体起源的更好理解，并评估在染色体和核苷酸水平的二级突变的谱。因此，我们使用染色体谱带，荧光原位杂交，单核苷酸多态性阵列和/或大规模平行测序（基因组，整个外显子组和转录组测序）方法研究了35位患者的42个肿瘤样品。我们确认了COL1A1 - PDGFB的起源与年龄相关的差异融合，并可能表明它在大多数情况下必须在DNA合成后产生，即在细胞周期的S或G2期。继发性染色体重排具有非随机模式，而单核苷酸变体似乎对肿瘤进展几乎没有影响。在低级和高级DPFT之间没有发现明显的基因组差异，但是在后者中，染色体数目和染色体失衡以及9p缺失的频率都倾向于更大。COL1A1 - PDGFB融合与不平衡易位或环状染色体相关的肿瘤的基因表达谱鉴定在染色体17和22的扩增区域中鉴定了几个转录上调的基因，包括TBX2，PRRKA，MSI2，SOX9，SOX10和PRAME。