Parafibromin Abnormalities in Ossifying Fibroma.
Parafibromin Abnormalities in Ossifying Fibroma.
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DOI：
10.1210/jendso/bvab087
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发表时间：
2021-07-01
影响因子：
4.1
通讯作者：
Arnold A
中科院分区：
文献类型：
--
作者：
Costa-Guda J;Pandya C;Strahl M;Taik P;Sebra R;Chen R;Uzilov AV;Arnold A
骨化纤维瘤是非常罕见的肿瘤，有时被视为甲状旁腺功能亢进症下颌肿瘤综合征 (HPT-JT) 的一部分，该综合征是由 HRPT2/CDC73 肿瘤抑制基因的失活突变引起的。 CDC73 突变已在部分散发病例中被发现，但编码蛋白副纤维蛋白的异常表达尚未在骨化纤维瘤中得到证实。我们试图确定副纤维蛋白的缺失是否经常导致散发性、非综合征性骨化纤维瘤的发展。我们检查了一系列 9 种骨化纤维瘤，包括骨化、牙骨质骨化和幼年活性变体，通过免疫组织化学检测副纤维蛋白表达，并通过 Sanger 测序和/或靶向 AmpliSeq panel 测序检测 CDC73 序列异常。四个骨化纤维瘤显示核副纤维蛋白表达完全缺失； 1 例中，副纤维蛋白表达缺失伴有细胞质副纤维蛋白表达异常。在 2 例副纤维蛋白表达异常的病例中检测到 CDC73 突变。这些结果在蛋白质表达水平上提供了新的证据，表明甲状旁腺CDC73/para纤维蛋白肿瘤抑制因子的缺失可能在骨化纤维瘤亚型的发病机制中发挥作用。
Ossifying fibromas are very rare tumors that are sometimes seen as part of the hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is caused by inactivating mutations of the HRPT2/CDC73 tumor suppressor gene. CDC73 mutations have been identified in a subset of sporadic cases but aberrant expression of the encoded protein, parafibromin, has not been demonstrated in ossifying fibroma. We sought to determine if loss of parafibromin regularly contributes to the development of sporadic, nonsyndromic ossifying fibroma. We examined a series of 9 ossifying fibromas, including ossifying, cemento-ossifying, and juvenile active variants, for parafibromin protein expression by immunohistochemistry and for CDC73 sequence abnormalities by Sanger sequencing and/or targeted AmpliSeq panel sequencing. Four ossifying fibromas showed a complete absence of nuclear parafibromin expression; loss of parafibromin expression was coupled with aberrant cytoplasmic parafibromin expression in 1 case. CDC73 mutations were detected in 2 cases with aberrant parafibromin expression. These results provide novel evidence, at the level of protein expression, that loss of the parathyroid CDC73/parafibromin tumor suppressor may play a role in the pathogenesis of a subset of ossifying fibromas.
影响因子：
3.7
作者：
Pazienza V;la Torre A;Baorda F;Alfarano M;Chetta M;Muscarella LA;Battista C;Copetti M;Kotzot D;Kapelari K;Al-Abdulrazzaq D;Perlman K;Sochett E;Cole DE;Pellegrini F;Canaff L;Hendy GN;D'Agruma L;Zelante L;Carella M;Scillitani A;Guarnieri V
通讯作者：
Guarnieri V