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首页> 外文期刊>Neoplasia: an international journal for oncology research >Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages
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Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

机译：双侧睾丸生殖细胞肿瘤的外壳测序表明了独立的发展谱系

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Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.
机译：睾丸生殖细胞肿瘤（TGCT）的前体肿瘤内胚细胞瘤瘤被假设以在从发育捕获的原始胚芽细胞（PGCs）或腺细胞的胚胎发生期间出现。在早期胚胎寿命中，PGCs从蛋黄囊迁移到背体壁，其中细胞群在殖民化生殖器脊之前分离。然而，在这种分离之前或之后，恶性转化是否发生争议。我们探索了双侧TGCT的体细胞突出的突变光谱，为恶性转化和TGCT发病机制提供了新的临界时间框架。在5例双侧TGCT（八种肿瘤）的患者中进行外壳测序，这三名患者（六种肿瘤）和两名患者只有一种可用的肿瘤（两种肿瘤）。在71例双侧TGCT患者中，Sanger测序探索了所选基因座。从偏心突变谱中，鉴定了三对双侧肿瘤对中的任何一种相同的突变。所有八种肿瘤的exome测序揭示了87个体细胞非同义突变（每个肿瘤中位数10;范围5-21），一些已知的癌症基因如CIITA，NEB，血小板衍生的生长因子受体α（PDGFRA）和WHSC1 。 Supt6h被发现在两种肿瘤中均匀突变。我们建议双边TGCT的独立开发谱系。因此，在PGC的迁移后可能发生恶性转化进入肠脉管胚芽细胞瘤形成。我们揭示了TGCT发病机制的可能驱动因素，例如突变的PDGFRA，可能具有对TGCT患者的治疗意义。

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