PBRM1 and BAP1: novel genetic mutations in malignant transformation of craniopharyngioma?a case report
PBRM1 and BAP1: novel genetic mutations in malignant transformation of craniopharyngioma?a case report
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PBRM1和BAP1：颅咽管瘤恶变的新基因突变？一例报告
DOI：
10.1007/s10014-022-00444-3
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发表时间：
2022
影响因子：
3.3
通讯作者：
Takeshima Hideo
中科院分区：
文献类型：
--
作者：
Tamura Mitsuru;Yokogami Kiyotaka;Watanabe Takashi;Kawano Tomoki;Muta Junichiro;Yamashita Shinji;Oguri Nobuyuki;Sato Yuichiro;Takeshima Hideo
恶性颅咽管瘤尤其罕见，因此与恶变相关的原因和基因突变尚未得到详细解释。我们研究了颅咽管瘤恶变的分子遗传学特征。一名 53 岁男性，有金刚质瘤性颅咽管瘤病史，主诉皮下肿胀。磁共振成像显示硬膜内鞍上病变增强程度较低，硬膜外侵入性病变不均匀强化，浸润硬脑膜、大脑、额骨和皮下组织。复发肿瘤的组织病理学检查显示颅咽管瘤（硬膜内鞍上病变）和恶变的典型表现，例如明显的核异型性伴有丝分裂（侵袭性硬膜外病变），而这些在原发肿瘤中并不存在。使用 Oncopanel 系统进行基因面板测试，以研究导致恶性转化的基因突变。鉴定出四种基因突变：CTNNB1c.C98T、TP53p.C135fs*35(PLS = 3 UPD/LOH)、PBRM1p.R1000*(PLS = 3 UPD/LOH)和BAP1p.L650fs*5(PLS = 3 UPD/LOH)。 Sanger测序显示CTNNB1在硬膜内鞍上和硬膜外浸润性病变中均有表达，而TP53、PBRM1和BAP1仅在硬膜外浸润性病变中表达。 PBRM1和BAP1基因突变可能是颅咽管瘤恶性转化的遗传因素。
Malignant craniopharyngioma is especially rare, so the causes and genetic mutations associated with the malignant transformation have not been explained in detail. We investigated the molecular genetic characteristics of malignant transformation in craniopharyngioma. A 53-year-old man with a history of adamantinomatous craniopharyngioma presented with complaints of subcutaneous swelling. Magnetic resonance imaging showed a less enhanced intradural supra-sellar lesion and a heterogeneously well-enhanced extradural invasive lesion infiltrating the dura mater, brain, frontal bone, and subcutaneous tissue. Histopathological examination of the recurrent tumor revealed typical findings of both craniopharyngioma (intradural supra-sellar lesion) and malignant transformation, such as marked nuclear atypia with mitosis (invasive extradural lesion), which were not present in the primary tumor. A genetic panel test with the Oncopanel system was performed to investigate the genetic mutations responsible for the malignant transformation. Four genetic mutations were identified:CTNNB1c.C98T,TP53p.C135fs*35(PLS = 3 UPD/LOH),PBRM1p.R1000*(PLS = 3 UPD/LOH), andBAP1p.L650fs*5(PLS = 3 UPD/LOH). Sanger sequencing showedCTNNB1in both the intradural supra-sellar and extradural invasive lesions, butTP53,PBRM1,andBAP1only in the extradural invasive lesion. The genetic mutations ofPBRM1andBAP1may be genetic factors in the malignant transformation of adamantinomatous craniopharyngioma.