Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas.
Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas.
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DOI：
10.3390/diagnostics11040681
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发表时间：
2021-04-09
期刊：
影响因子：
--
通讯作者：
Fujii Y
中科院分区：
文献类型：
--
作者：
On J;Natsumeda M;Watanabe J;Saito S;Kanemaru Y;Abe H;Tsukamoto Y;Okada M;Oishi M;Yoshimura J;Kakita A;Fujii Y
最近的研究表明，在弥漫性中线胶质瘤（DMG）患者脑脊液中检测H3K27M突变是可行的。然而，这些研究中患者的脑脊液主要是在活检、脑室-腹膜分流术或死后收集的。我们评估了从12例影像学怀疑和/或病理证实的弥漫性中线胶质瘤患者的脑脊液（CSF）和血浆中提取的循环肿瘤DNA (ctDNA)，并使用数字液滴PCR评估了H3F3A K27M突变。10例患者在就诊时通过腰椎穿刺获得脑脊液。H3F3A K27M突变仅在1例（10%）中得到明确检测；另外3例（30%）疑似H3F3A K27M突变。在脑室-腹膜分流术治疗梗阻性脑积水的两例患者脑脊液中检测到H3F3A K27M突变。与不明确的病例相比，可能进行明确评估的病例（明确的H3F3A K27M或明确的H3F3A野生型）往往更年轻（中位7.5岁对40.5岁，p = 0.07），脑脊液蛋白浓度更高（中位123 mg/dL对27.5 mg/dL, p = 0.21）。低增殖率和凋亡率似乎是DMG的特征，对液体活检不利。由于担心加重梗阻性脑积水，更晚期的坏死和播散性病变不太可能成为腰椎穿刺的候选者。安全的CSF取样方法和更灵敏的ctDNA检测是DMG出现时可靠的液体活检的必要条件。
Recent studies have suggested the feasibility of detecting H3K27M mutations in the cerebrospinal fluid of diffuse midline glioma (DMG) patients. However, cerebrospinal fluid from patients in these studies were collected mainly during biopsy, ventriculo-peritoneal shunt procedures or postmortem. We assessed circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF) and plasma in a series of 12 radiographically suspected and/or pathologically confirmed diffuse midline glioma patients and assessed for H3F3A K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of H3F3A K27M mutation was achieved in only one case (10%); H3F3A K27M mutation was suspected in three other cases (30%). H3F3A K27M mutation was detected in two patients in CSF obtained by ventricular tap during a ventriculo-peritoneal shunt for obstructive hydrocephalus. Cases in which a definitive assessment was possible (definite H3F3A K27M or definite H3F3A wildtype) tended to be younger (median 7.5 years vs. 40.5 years; p = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; p = 0.21) compared to nondefinite cases. Low proliferation and apoptotic rates seemed to be characteristics of DMG unfavorable for liquid biopsy. More advanced lesions with necrosis and evidence of dissemination were unlikely to be candidates for lumbar puncture due to the fear of exacerbating obstructive hydrocephalus. Methods to safely sample CSF and a more sensitive detection of ctDNA are necessary for reliable liquid biopsy of DMG at presentation.
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DOI：
10.1158/1078-0432.ccr-18-1345
发表时间：
2018-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Panditharatna E;Kilburn LB;Aboian MS;Kambhampati M;Gordish-Dressman H;Magge SN;Gupta N;Myseros JS;Hwang EI;Kline C;Crawford JR;Warren KE;Cha S;Liang WS;Berens ME;Packer RJ;Resnick AC;Prados M;Mueller S;Nazarian J
通讯作者：
Nazarian J
影响因子：
30.8
作者：
Wu G;Diaz AK;Paugh BS;Rankin SL;Ju B;Li Y;Zhu X;Qu C;Chen X;Zhang J;Easton J;Edmonson M;Ma X;Lu C;Nagahawatte P;Hedlund E;Rusch M;Pounds S;Lin T;Onar-Thomas A;Huether R;Kriwacki R;Parker M;Gupta P;Becksfort J;Wei L;Mulder HL;Boggs K;Vadodaria B;Yergeau D;Russell JC;Ochoa K;Fulton RS;Fulton LL;Jones C;Boop FA;Broniscer A;Wetmore C;Gajjar A;Ding L;Mardis ER;Wilson RK;Taylor MR;Downing JR;Ellison DW;Zhang J;Baker SJ
通讯作者：
Baker SJ
影响因子：
12.7
作者：
Castel D;Philippe C;Calmon R;Le Dret L;Truffaux N;Boddaert N;Pagès M;Taylor KR;Saulnier P;Lacroix L;Mackay A;Jones C;Sainte-Rose C;Blauwblomme T;Andreiuolo F;Puget S;Grill J;Varlet P;Debily MA
通讯作者：
Debily MA
DOI：
10.1097/nen.0000000000000216
发表时间：
2015-08
影响因子：
3.2
作者：
Taylor IC;Hütt-Cabezas M;Brandt WD;Kambhampati M;Nazarian J;Chang HT;Warren KE;Eberhart CG;Raabe EH
通讯作者：
Raabe EH
影响因子：
1.9
作者：
Abe H;Natsumeda M;Kanemaru Y;Watanabe J;Tsukamoto Y;Okada M;Yoshimura J;Oishi M;Fujii Y
通讯作者：
Fujii Y