Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas
Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas
复制标题
恶性甲状腺畸胎瘤中的复发性 DICER1 热点突变
DOI：
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发表时间：
2020
影响因子：
5.6
通讯作者：
J. Bishop
中科院分区：
文献类型：
--
作者：
L. Rooper;J. Bynum;Karin Miller;Ming;J. Gagan;L. Thompson;J. Bishop
甲状腺畸胎瘤是一种罕见的肿瘤，其临床病理范围很广。虽然良性和未成熟畸胎瘤出现在婴儿和幼儿，通常有良好的结果，恶性畸胎瘤影响成人，并遵循积极的过程。这种不同的行为增加了良性/未成熟畸胎瘤和恶性畸胎瘤是独立实体的可能性，而不是单个肿瘤的不同级别。然而，无论级别如何，甲状腺畸胎瘤的组织发生和分子基础都知之甚少。在本研究中，我们对8例甲状腺畸胎瘤进行了下一代测序，其中4例为恶性，3例为良性，1例为未成熟畸胎瘤。我们在所有4例恶性病例（100%）中发现了DICER1热点突变，但没有在任何良性/不成熟病例（0%）中发现DICER1热点突变。两组患者均未发现其他基因有临床意义的突变。我们还进行了免疫组织化学表征恶性畸胎瘤的原始成分。所有病例不仅一致含有未成熟的神经成分（synaptophysin和INSM1阳性），而且也含有横纹肌母细胞分化的纺锤体细胞（desmin和myogenin阳性）和甲状腺滤泡源性的温和上皮增生（TTF-1和PAX8阳性）。虽然DICER1突变先前与多结节增生和分化良好的甲状腺癌有关，但这些发现表明DICER1在原始甲状腺肿瘤中首次复发。在这一系列恶性甲状腺畸胎瘤中突出的神经、横纹肌母细胞和同源上皮成分与其他器官中dicer1突变肿瘤的成分相似。总的来说，这些分子发现进一步扩大了良性/未成熟畸胎瘤和恶性畸胎瘤之间的差异，支持将这些肿瘤分类为独立的实体。
Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities.
影响因子：
120.7
作者：
Frio, Thomas Rio;Bahubeshi, Amin;Kanellopoulou, Chryssa;Hamel, Nancy;Niedziela, Marek;Sabbaghian, Nelly;Pouchet, Carly;Gilbert, Lucy;O'Brien, Paul K.;Serfas, Kim;Broderick, Peter;Houlston, Richard S.;Lesueur, Fabienne;Bonora, Elena;Muljo, Stefan;Schimke, R. Neil;Bouron-Dal Soglio, Dorothee;Arseneau, Jocelyne;Schultz, Kris Ann;Priest, John R.;Nguyen, Van-Hung;Ruben Harach, H.;Livingston, David M.;Foulkes, William D.;Tischkowitz, Marc
通讯作者：
Tischkowitz, Marc
影响因子：
5.8
作者：
Rutter, Meilan M.;Jha, Pranati;Hill, D. Ashley
通讯作者：
Hill, D. Ashley
影响因子：
10.5
作者：
Kumar, Madhu S.;Pester, Ryan E.;Jacks, Tyler
通讯作者：
Jacks, Tyler