Department of Pathology, Taipei Veterans General Hospital and National Yang-Ming University, 11217 Taiwan.
Department of Surgical Pathology, Aichi Medical University, School of Medicine, 480-1195 Japan.
Hum Pathol. 2018 Jun;76:9-16. doi: 10.1016/j.humpath.2017.12.004. Epub 2017 Dec 16.
In a previous array comparative genomic hybridization study, we detected common deletions of chromosomes 13 and 14 in prostatic stromal sarcoma and stromal tumor of uncertain malignant potential (STUMP). In this study, we performed whole-exome sequencing (WES) and fluorescence in situ hybridization to explore somatic mutations in 1 low-grade stromal sarcoma, 1 high-grade stromal sarcoma, and 12 STUMPs including 5 cases of degenerative atypia type, 1 myxoid type, 1 phyllodes type, and 5 cases of recently described round cell type. WES was successful on 13 cases that revealed frequent somatic copy number alterations including losses of chromosomes 13 (11 cases), 14 (11 cases), and 1p (9 cases), and partial or complete loss of chromosome 10 (7 cases). Fluorescence in situ hybridization was done on 9 cases and showed compatible chromosome 13 copy numbers with the WES results. STUMPs and the low-grade stromal sarcoma carried moderate tumor mutation burdens that ranged from 1.23 to 7.24 mutations per megabase, while the high-grade stromal sarcoma harbored a significantly higher mutation burden (11.55 mutations per megabase). Sporadic somatic mutations were observed, but no recurrent driver mutations could be discerned. In conjunction with prior array comparative genomic hybridization, we have demonstrated the consistent gene dosage profiles that support the clonal nature and the concept of specialized stromal tumors of the prostate as a distinctive tumor entity.
在之前的一项比较基因组杂交阵列研究中，我们在前列腺基质肉瘤和不确定恶性潜能的基质肿瘤（STUMP）中检测到染色体 13 和 14 的常见缺失。在这项研究中，我们进行了全外显子组测序（WES）和荧光原位杂交，以探索 1 例低度基质肉瘤、1 例高度基质肉瘤和 12 例 STUMP 中的体细胞突变，其中包括 5 例退行性异型性、1 例黏液样型、1 例叶状型和 5 例最近描述的圆形细胞型。WES 在 13 例中成功进行，揭示了频繁的体细胞拷贝数改变，包括染色体 13（11 例）、14（11 例）和 1p（9 例）的丢失，以及染色体 10 的部分或完全缺失（7 例）。荧光原位杂交在 9 例中进行，显示与 WES 结果相符的染色体 13 拷贝数。STUMPs 和低度基质肉瘤携带中等肿瘤突变负担，范围从每兆碱基 1.23 到 7.24 个突变，而高度基质肉瘤则携带明显更高的突变负担（每兆碱基 11.55 个突变）。观察到散在的体细胞突变，但无法识别出复发性驱动突变。结合之前的比较基因组杂交阵列，我们展示了一致的基因剂量谱，支持前列腺特化基质肿瘤的克隆性质和概念，作为一个独特的肿瘤实体。
