Targeted next-generation sequencing of cancer genes identified frequent TP53 and ATRX mutations in leiomyosarcoma.
Targeted next-generation sequencing of cancer genes identified frequent TP53 and ATRX mutations in leiomyosarcoma.
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癌症基因的下一代靶向测序发现了平滑肌肉瘤中常见的 TP53 和 ATRX 突变。
DOI：
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发表时间：
2015
影响因子：
2.2
通讯作者：
Y. Jeng
中科院分区：
文献类型：
--
作者：
Ching;Jau;Wei;Yu;Ming‐Chu Chang;Jen;J. Tsai;Yidi Su;Chia;Y. Jeng
平滑肌肉瘤是一种侵袭性软组织肉瘤，患者生存率低。平滑肌肉瘤的遗传学改变仍有待发现。在这项研究中，我们分析了44个癌症相关基因的遗传变化，通过使用新一代测序在54个平滑肌瘤。我们在54例肿瘤中的19例（35%）中发现了TP 53突变，在54例肿瘤中的9例（17%）中发现了ATRX突变。TP 53突变的平滑肌瘤仅限于女性患者（P = 0.006）。除了2例TP 53突变的平滑肌瘤外，其余均位于子宫（n = 11）或腹膜后（n = 6）。ATRX突变与低分化平滑肌瘤（P = 0.028）和肿瘤坏死（P = 0.015）相关。Kaplan-Meier生存分析显示ATRX突变型平滑肌瘤患者的总体生存率低于ATRX野生型平滑肌瘤患者。所有ATRX突变的平滑肌瘤都表现出端粒延长的表型。ATRX突变与ATRX蛋白表达无关，如使用免疫组织化学检测到的。总之，我们确定了p53和ATRX通路的功能丧失是平滑肌瘤的主要机制。分子机制可能为治疗这些侵袭性肿瘤提供新的机会。
Leiomyosarcoma is an aggressive soft tissue sarcoma with poor patient survival. The genetic changes of leiomyosarcoma remain to be discovered. In this study, we analyzed the genetic changes of 44 cancer-related genes by using next-generation sequencing in 54 leiomyosarcomas. We identified TP53 mutations in 19 of the 54 tumors (35%) and ATRX mutations in 9 of the 54 tumors (17%). The TP53-mutated leiomyosarcomas were limited to female patients (P = 0.006). All but 2 of the TP53-mutated leiomyosarcomas were located in the uterus (n = 11) or retroperitoneum (n = 6). The ATRX mutations were associated with poorly differentiated leiomyosarcomas (P = 0.028) and the presence of tumor necrosis (P = 0.015). Kaplan-Meier survival analysis showed that patients with ATRX-mutated leiomyosarcomas had worse overall survival than did patients with ATRX-wild-type leiomyosarcomas. All of the ATRX-mutated leiomyosarcomas showed the alternative lengthening of telomere phenotype. The ATRX mutations did not correlate with ATRX protein expression, as detected using immunohistochemistry. In conclusion, we identified loss of function of the p53 and ATRX pathways being the main mechanisms for leiomyosarcomas. The molecular mechanisms may provide new opportunities to treat these aggressive neoplasms.
成人软组织肉瘤中 17 号染色体异常和 TP53 突变。
DOI：
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发表时间：
1994
期刊：
The American journal of pathology
影响因子：
--
作者：
Latres,E;Drobnjak,M;Pollack,D;Oliva,MR;Ramos,M;Karpeh,M;Woodruff,JM;Cordon-Cardo,C
通讯作者：
Cordon-Cardo,C
影响因子：
10.5
作者：
PAVLETICH, NP;CHAMBERS, KA;PABO, CO
通讯作者：
PABO, CO
影响因子：
45.3
作者：
Hensley, ML;Maki, R;Spriggs, DR
通讯作者：
Spriggs, DR