Lee Paul J, Yoo Naomi S, Hagemann Ian S, Pfeifer John D, Cottrell Catherine E, Abel Haley J, Duncavage Eric J
Department of Pathology and Immunology, Washington University, St. Louis, MO, United States.
Department of Genetics, Washington University, St. Louis, MO, United States.
Exp Mol Pathol. 2017 Feb;102(1):156-161. doi: 10.1016/j.yexmp.2017.01.012. Epub 2017 Jan 14.
Recurrent genomic mutations in uterine and non-uterine leiomyosarcomas have not been well established. Using a next generation sequencing (NGS) panel of common cancer-associated genes, 25 leiomyosarcomas arising from multiple sites were examined to explore genetic alterations, including single nucleotide variants (SNV), small insertions/deletions (indels), and copy number alterations (CNA). Sequencing showed 86 non-synonymous, coding region somatic variants within 151 gene targets in 21 cases, with a mean of 4.1 variants per case; 4 cases had no putative mutations in the panel of genes assayed. The most frequently altered genes were TP53 (36%), ATM and ATRX (16%), and EGFR and RB1 (12%). CNA were identified in 85% of cases, with the most frequent copy number losses observed in chromosomes 10 and 13 including PTEN and RB1; the most frequent gains were seen in chromosomes 7 and 17. Our data show that deletions in canonical cancer-related genes are common in leiomyosarcomas. Further, the spectrum of gene mutations observed shows that defects in DNA repair and chromosomal maintenance are central to the biology of leiomyosarcomas, and that activating mutations observed in other common cancer types are rare in leiomyosarcomas.
子宫和非子宫平滑肌肉瘤中反复出现的基因组突变尚未完全明确。利用一个包含常见癌症相关基因的二代测序（NGS）面板，对来自多个部位的25例平滑肌肉瘤进行检测，以探索基因改变，包括单核苷酸变异（SNV）、小插入/缺失（indels）和拷贝数改变（CNA）。测序显示，21例病例的151个基因靶点中有86个非同义编码区体细胞变异，平均每例有4.1个变异；4例在检测的基因面板中无假定突变。最常发生改变的基因是TP53（36%）、ATM和ATRX（16%），以及EGFR和RB1（12%）。85%的病例检测到CNA，10号和13号染色体上观察到最常见的拷贝数缺失，包括PTEN和RB1；7号和17号染色体上观察到最常见的拷贝数增加。我们的数据表明，在平滑肌肉瘤中，经典癌症相关基因的缺失很常见。此外，观察到的基因突变谱表明，DNA修复和染色体维持缺陷是平滑肌肉瘤生物学特性的核心，而在其他常见癌症类型中观察到的激活突变在平滑肌肉瘤中很少见。
