Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data.
Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data.
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DOI：
10.3390/cancers13102389
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发表时间：
2021-05-14
期刊：
影响因子：
5.2
通讯作者：
Chun SM
中科院分区：
文献类型：
--
作者：
Choi YM;Lim J;Jeon MJ;Lee YM;Sung TY;Hong EG;Lee JY;Jang SJ;Kim WG;Song DE;Chun SM
嗜铬细胞瘤和副神经节瘤(PPGL)分别是起源于肾上腺髓质嗜铬细胞或肾上腺外副神经节的神经内分泌肿瘤。在PPGLS中，高达60%的患者发现了已知易感基因之一的种系或体细胞突变。世界卫生组织最近的分类定义了所有PPGL都可能有转移潜能。在这组肿瘤中，“恶性”一词被“转移性”所取代。然而，驱动PPGL侵袭性行为的特殊遗传事件，包括PPGL中的转移，目前还知之甚少。我们进行了有针对性的下一代测序分析，以表征15名侵袭性PPGL患者的突变情况，并将来自癌症基因组图谱(TCGA)的侵袭性PPGL的可访问数据与我们队列的发现进行了比较。这种有针对性的突变分析可能扩大侵袭性PPGL的突变谱，也可能有助于检测可能的实验性治疗方案或预测不良预后。在嗜铬细胞瘤和副神经节瘤(PPGL)中，高达60%的患者发现了已知易感基因之一的胚系或体细胞突变。然而，PPGL中驱动包括转移在内的侵袭性行为的特殊遗传事件却知之甚少。我们进行了有针对性的下一代测序分析，以表征15名侵袭性PPGL患者的突变情况，并将来自癌症基因组图谱(TCGA)的侵袭性PPGL的可访问数据与我们队列的发现进行了比较。在我们的队列中，共有115个种系和34个体细胞变异被鉴定，平均每兆碱基肿瘤突变负担为0.58。最常见的突变是SDHB种系突变(27%)，其次是SETD2、NF1和HRAS的体细胞突变(分别为13%)。根据突变基因的种类，患者被分成三种类型：假性缺氧组(n=5)、激酶组(n=5)和未知组(n=5)。在拷贝数变异分析中，最常见的是含有SDHB基因的染色体臂1p的缺失。在我们的队列中，SDHB突变和假性缺氧亚型与较差的总体存活率显著相关。结论：对预后不同的侵袭性PPGL患者，突变谱分型有助于制定相应的随访计划，达到合理治疗的目的。
Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from chromaffin cells of the adrenal medulla, or extra-adrenal paraganglia, respectively. In PPGLs, germline or somatic mutations in one of the known susceptibility genes are identified in up to 60% patients. Recent WHO classification defines that all PPGLs can have metastatic potential. The term, ‘malignant’ is replaced with ‘metastatic’ in this group of tumors. However, the peculiar genetic events that drive the aggressive behavior, including metastasis in PPGLs are yet poorly understood. We performed targeted next-generation sequencing analysis to characterize the mutation profile in fifteen aggressive PPGL patients and compared accessible data of aggressive PPGLs from The Cancer Genome Atlas (TCGA) with findings of our cohort. This targeted mutational analysis might expand the mutation profile of aggressive PPGLs, and may also be useful in detecting the possible experimental therapeutic options or predicting poor prognosis. In pheochromocytoma and paraganglioma (PPGL), germline or somatic mutations in one of the known susceptibility genes are identified in up to 60% patients. However, the peculiar genetic events that drive the aggressive behavior including metastasis in PPGL are poorly understood. We performed targeted next-generation sequencing analysis to characterize the mutation profile in fifteen aggressive PPGL patients and compared accessible data of aggressive PPGLs from The Cancer Genome Atlas (TCGA) with findings of our cohort. A total of 115 germline and 34 somatic variants were identified with a median 0.58 per megabase tumor mutation burden in our cohort. The most frequent mutation was SDHB germline mutation (27%) and the second frequent mutations were somatic mutations for SETD2, NF1, and HRAS (13%, respectively). Patients were subtyped into three categories based on the kind of mutated genes: pseudohypoxia (n = 5), kinase (n = 5), and unknown (n = 5) group. In copy number variation analysis, deletion of chromosome arm 1p harboring SDHB gene was the most frequently observed. In our cohort, SDHB mutation and pseudohypoxia subtype were significantly associated with poor overall survival. In conclusion, subtyping of mutation profile can be helpful in aggressive PPGL patients with heterogeneous prognosis to make relevant follow-up plan and achieve proper treatment.
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影响因子：
50.3
作者：
Fishbein L;Leshchiner I;Walter V;Danilova L;Robertson AG;Johnson AR;Lichtenberg TM;Murray BA;Ghayee HK;Else T;Ling S;Jefferys SR;de Cubas AA;Wenz B;Korpershoek E;Amelio AL;Makowski L;Rathmell WK;Gimenez-Roqueplo AP;Giordano TJ;Asa SL;Tischler AS;Cancer Genome Atlas Research Network;Pacak K;Nathanson KL;Wilkerson MD
通讯作者：
Wilkerson MD
影响因子：
4
作者：
Curras-Freixes, Maria;Inglada-Perez, Lucia;Robledo, Mercedes
通讯作者：
Robledo, Mercedes
影响因子：
3.5
作者：
Castro-Vega, Luis Jaime;Buffet, Alexandre;Gimenez-Roqueplo, Anne-Paule
通讯作者：
Gimenez-Roqueplo, Anne-Paule
影响因子：
3.2
作者：
CASANOVA, S;ROSENBERGBOURGIN, M;MODIGLIANI, E
通讯作者：
MODIGLIANI, E
影响因子：
30.8
作者：
Comino-Mendez, Inaki;Gracia-Aznarez, Francisco J.;Cascon, Alberto
通讯作者：
Cascon, Alberto