High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.
High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.
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DOI：
10.1111/cas.15256
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发表时间：
2022-03
期刊：
影响因子：
5.7
通讯作者：
Takeuchi K
中科院分区：
文献类型：
--
作者：
Kunieda J;Yamashita K;Togashi Y;Baba S;Sakata S;Inamura K;Ae K;Matsumoto S;Machinami R;Kitagawa M;Takeuchi K
黏液样脂肪肉瘤(MLP)是一种以FUS-DDIT3或EWSR1-DDIT3基因融合和编码TERT蛋白的端粒酶逆转录酶(TERT)启动子区高频率热点突变(C228T或C250T)为特征的遗传病。后者导致端粒酶重新激活，端粒维持的一种机制。尽管TERT启动子热点突变在多种肿瘤中是一个预后不良的因素，但其对MLP的影响尚未有详细的报道。在本研究中，我们研究了2008年至2020年在日本东京癌症研究基金会癌症研究所医院手术切除的83例MLP的临床病理特征、预后和端粒维持机制。77%(63/82)的病例发现TERT启动子热点突变，所有病例均未发现端粒交替延长(ALT)。在无TERT启动子热点突变的病例中，3例TERT重排，2例TERT启动子区域的微小点突变。即使在没有检测到基因组TERT异常的患者中，TERT mRNA的表达也是一致的，并且TERT启动子热点突变的存在与总体和无转移生存期(分别为P=5.56，P=8.83)或临床病理特征均无显著相关性。因此，MLP患者具有特征性的TERT表达和高发生率的TERT异常。我们的研究结果表明，TERT异常不是预后因素，但可能发生在早期阶段，并在肿瘤发生中发挥关键作用。在这项研究中，我们在大量的MLP病例中研究了两种类型的端粒维持机制，并研究了MLP患者端粒维持机制与疾病预后或临床病理参数的关系。他们的发现表明，TERT异常不是预后因素，但可能发生在早期阶段，并在肿瘤发生中发挥关键作用。
Myxoid liposarcoma (MLPS) is genetically characterized by FUS‐DDIT3 or EWSR1‐DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis‐free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis. In this study, we investigated the 2 types of telomere maintenance mechanisms in a large cohort of MLPS cases and examined the relationship between the telomere maintenance mechanism and disease prognosis or clinicopathological parameters in patients with MLPS. Their findings suggest that TERT aberrations are not prognostic factors, but might occur at an early stage and play key roles in tumorigenesis.
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DOI：
10.1002/cjp2.16
发表时间：
2015-07
期刊：
The journal of pathology. Clinical research
影响因子：
--
作者：
Iura K;Kohashi K;Hotokebuchi Y;Ishii T;Maekawa A;Yamada Y;Yamamoto H;Iwamoto Y;Oda Y
通讯作者：
Oda Y
31种癌症类型的端粒长度和躯体改变的系统分析。
影响因子：
30.8
作者：
Barthel FP;Wei W;Tang M;Martinez-Ledesma E;Hu X;Amin SB;Akdemir KC;Seth S;Song X;Wang Q;Lichtenberg T;Hu J;Zhang J;Zheng S;Verhaak RG
通讯作者：
Verhaak RG
影响因子：
3.5
作者：
Gaspar TB;Sá A;Lopes JM;Sobrinho-Simões M;Soares P;Vinagre J
通讯作者：
Vinagre J
影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
3.9
作者：
Dwight, Trisha;Flynn, Aidan;Tothill, Richard W.
通讯作者：
Tothill, Richard W.