SCAPER-NTRK2融合突變成人高級(jí)別星形細(xì)胞瘤1例報(bào)告 并文獻(xiàn)復(fù)習(xí)

【中圖分類號(hào)】 R739.41 【文獻(xiàn)標(biāo)志碼】B 【文章編號(hào)】1672-7770（2025）03-0356-05

Abstract：ObjectiveTo explore the molecular features of glioma with NTRK fusionand the effectiveness of Stuppregimen for newlydiagnosed high-grade gliomas withNTRK fusion mutations.MethodsTheclinical dataof oneadulthigh-gradeglioma with SCAPER-NTRK2mutationadmittedto Affiliated HospitalofJining Medical Universityin March2O23wereanalyzedretrospectively.The immunohistochemistryand molecular testing were used， andthe relevantliterature were reviewed.ResultsThe cranial MRI suggesteda tumorous lesion in the left parietal temporal lobe.Surgical resection of the tumour was folowed by simultaneous Stupp regimen treatment.Genetic testing of tumour tissue IIshowed IDH1 P.R132H exon 4 missense mutation，NTRK2（SCAPER-NTRK2） fusion mutation， CDKN2A/2B copy number deletion.At 13-month follw-up，there were no signs andsymptoms of neurological deficits，and there were no signs of recurrence of the tumour on repeat cranial MRI. ConclusionsThe Stupp regimenis an efective treatment option for newlydiagnosed high-grade glioma with NTRK2 fusion mutations，and second-generation genetic testing is recommended as the preferred test for NTRK gene fusions.

Key Words：NTRK fusion；astrocytoma；Stupp regimen；CDKN2A/B；pathological diagnosis

星形細(xì)胞瘤是中樞神經(jīng)系統(tǒng)最常見(jiàn)的原發(fā)性惡性腫瘤之一。目前認(rèn)為，神經(jīng)營(yíng)養(yǎng)因子受體絡(luò)氨酸激酶（neurotrophinreceptorkinase，NTRK）融合突變是中樞神經(jīng)系統(tǒng)腫瘤的一個(gè)罕見(jiàn)但有治療價(jià)值的靶點(diǎn)[1-2]。膠質(zhì)瘤患者NTRK融合突變檢出率低于 1% ，其中NTRK2融合更為罕見(jiàn)[3]。NTRK融合突變是多種成人和兒童腫瘤的致癌驅(qū)動(dòng)因子[1，4]。NTRK基因融合是通過(guò)染色體內(nèi)或染色體間重排將NTRK1/2/3的 3^′ 序列（編碼完整的激酶結(jié)構(gòu)域）與伴侶基因的 5^′ 序列（編碼寡聚化或其他蛋白結(jié)合結(jié)構(gòu)域）鏈接，產(chǎn)生處于持續(xù)活躍狀態(tài)的TRK融合蛋白而成為真正的致癌驅(qū)動(dòng)因子[1，4]。自從發(fā)現(xiàn)異檸檬酸脫氫酶（isocitratedehydrogenase，IDH）突變?cè)趶浡阅z質(zhì)瘤的發(fā)病機(jī)制和預(yù)后中的重要性以來(lái)，星形細(xì)胞瘤的分類發(fā)生了演變。2021年第5版世界衛(wèi)生組織（WorldHealthOrganization，WHO）中樞神經(jīng)系統(tǒng)腫瘤分類將成人星形細(xì)胞瘤分為IDH突變型和IDH野生型星形細(xì)胞瘤，根據(jù)形態(tài)學(xué)和基因的改變又將IDH突變型星形細(xì)胞瘤分為Ⅱ級(jí)、Ⅲ級(jí)和V級(jí)[5]。IDH突變型IV級(jí)星形細(xì)胞瘤表現(xiàn)為細(xì)胞壞死、微血管增生或CDKN2A/2B同源染色體缺失[]。因此，分子病理對(duì)評(píng)估星形細(xì)胞瘤的分級(jí)和預(yù)后至關(guān)重要。隨著二代測(cè)序（nextgenerationsequencing，NGS）檢測(cè)技術(shù)的發(fā)展，越來(lái)越多的罕見(jiàn)NTRK融合突變患者被檢測(cè)出來(lái)，本文現(xiàn)報(bào)道濟(jì)寧醫(yī)學(xué)院附屬醫(yī)院2023年3月收治的1例罕見(jiàn)的伴NTRK2融合、IDH1突變、CDKN2A/2B拷貝數(shù)缺失的成人WHOV級(jí)星形細(xì)胞瘤患者，分析其分子特征并結(jié)合相關(guān)文獻(xiàn)，探討NTRK2融合基因的作用機(jī)制和Stupp治療方案的有效性，為臨床治療NTRK融合突變高級(jí)別膠質(zhì)瘤積累經(jīng)驗(yàn)。……