Saito Tsuyoshi, Akaike Keisuke, Kurisaki-Arakawa Aiko, Toda-Ishii Midori, Mukaihara Kenta, Suehara Yoshiyuki, Takagi Tatsuya, Kaneko Kazuo, Yao Takashi
Department of Human Pathology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Department of Human Pathology, Juntendo University School of Medicine, Tokyo 113-8421, Japan; Department of Orthopaedic Surgery, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Mol Clin Oncol. 2016 Jan;4(1):61-64. doi: 10.3892/mco.2015.674. Epub 2015 Nov 9.
Recurrent hot-spot mutations in the telomerase reverse transcriptase () promoter have been reported in various types of tumor. In several tumor types, promoter mutations are associated with poor clinical outcomes. promoter mutations are reported to be rare in soft tissue tumors, with the exception of myxoid liposarcoma (MLS). Our previous study reported that promoter mutations occurred in a subset of solitary fibrous tumors (SFTs) and were associated with adverse clinical outcomes in Japanese individuals. The site-specific frequency (e.g. central nervous or soft tissue origin) of promoter mutations in our SFT cases appeared to be different from previously reported values in a European population. These findings prompted the present study to elucidate the potential role of ethnic background in the different frequencies of promoter mutations in bone and soft tissue sarcomas. In the present study, promoter mutations were examined in 180 cases of bone and soft tissue sarcomas. promoter region mutations were identified in 10 cases [5 SFTs, 3 MLSs, 1 undifferentiated pleomorphic sarcoma (UPS) and 1 malignant granular cell tumor]. All mutations were C228T. The frequencies of promoter mutation in MLS and UPS were 23.1 (3/13) and 5% (1/20), respectively. Only 1/5 patients with -mutated tumors experienced local recurrence or distant metastasis. The present study revealed the first case of a malignant granular cell tumor with a promoter mutation and revealed that the frequency of promoter mutations in MLSs of Japanese patients is lower compared with that reported in German patients, providing evidence of a possible ethnic difference in the frequency of promoter mutations.
在各种类型的肿瘤中均已报道端粒酶逆转录酶（）启动子存在复发性热点突变。在几种肿瘤类型中，启动子突变与不良临床预后相关。据报道，除黏液样脂肪肉瘤（MLS）外，启动子突变在软组织肿瘤中较为罕见。我们之前的研究报道，在一部分孤立性纤维瘤（SFT）中发生了启动子突变，且在日本人群中与不良临床预后相关。我们SFT病例中启动子突变的位点特异性频率（如中枢神经或软组织起源）似乎与欧洲人群先前报道的值不同。这些发现促使本研究阐明种族背景在骨肉瘤和软组织肉瘤中启动子突变频率差异中的潜在作用。在本研究中，对180例骨肉瘤和软组织肉瘤病例检测了启动子突变。在10例病例中鉴定出启动子区域突变[5例SFT、3例MLS、1例未分化多形性肉瘤（UPS）和1例恶性颗粒细胞瘤]。所有突变均为C228T。MLS和UPS中启动子突变的频率分别为23.1%（3/13）和5%（1/20）。只有1/5的启动子突变肿瘤患者发生了局部复发或远处转移。本研究首次报道了1例具有启动子突变的恶性颗粒细胞瘤，并揭示日本患者MLS中启动子突变的频率低于德国患者报道的频率，为启动子突变频率可能存在种族差异提供了证据。
