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TERT プロモーターの変異が髄膜腫の結果を予測する影響:複数の機関によるコホート分析

Karenna J Groff ¹, Ruchit V Patel ², Yang Feng ³

¹Department of Neurosurgery, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA; Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.
²Department of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, MA, USA.
³Department of Biostatistics, NYU School of Global Public Health, New York, NY, USA.
⁴Department of Neurosurgery, Mass General Brigham and Harvard Medical School, Boston, MA, USA; Division of Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Boston, MA, USA.
⁵Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
⁶Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
⁷Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
⁸Department of Neurosurgery, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.
⁹Department of Neurological Surgery, Northwestern University, Chicago, IL, USA.
¹⁰Department of Radiation Oncology, Mass General Brigham and Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Charité Universitätsmedizin Berlin Hospital with Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK) Partner Site Berlin, Berlin, Germany.
¹¹MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre at University Health Network and University of Toronto, Toronto, ON, Canada; Division of Neurosurgery, University of Toronto, Toronto, ON, Canada.
¹²Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹³Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK) and German Cancer Research Center (DFKZ), Heidelberg, Germany.
¹⁵Department of Pediatric Hematology and Oncology and Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
¹⁶Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁷Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
¹⁸Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁹Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²⁰MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre at University Health Network and University of Toronto, Toronto, ON, Canada; Division of Neurosurgery, University of Toronto, Toronto, ON, Canada; Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
²¹Department of Radiation Oncology, Charité Universitätsmedizin Berlin Hospital with Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK) Partner Site Berlin, Berlin, Germany; Department of Radiation Oncology, Health and Medical University Potsdam, Potsdam, Germany.
²²Department of Neuropathology, Charité Universitätsmedizin Berlin Hospital with Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK) Partner Site Berlin, Berlin, Germany.
²³Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA; Department of Otolaryngology, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
²⁴Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; UCSF Brain Tumor Center and Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
²⁵Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA; The Chênevert Family Brain Tumor Center, Smilow Cancer Hospital, New Haven, CT, USA.
²⁶Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.

⁰Department of Neurosurgery, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA; Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.

The Lancet. Oncology +

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2025年9月4日

PubMedで要約を見る

まとめ

熱帯膜腫におけるTERTプロモーター変異は,常に攻撃的な腫瘍を示すわけではありません. CDKN2A/Bの喪失は,特にWHOの2級髄膜腫の予後における重要な要因である.

科学分野

神経腫瘍学
分子病理学
ゲノミクス

背景

分子変異は,髄膜腫の分類にますます使用されています.
TERTプロモーター (TERTp) 変異は,より悪い予後とWHOのグレード3指定に関連しています.
TERTp変異の予後効果は,同時に発生する遺伝的変異に依存する可能性があります.

研究の目的

髄膜腫の予後におけるTERTp変異の役割を調査する.
TERTpの変異が文脈に依存するかどうかを判断する.
臨床的な有用性のためにTERTpの配列決定をガイドする.

主な方法

多様性プロファイルの1492人の髄膜腫患者の分析
TERTpの変異,CDKN2A/Bの喪失,コピー数の変化の評価
カプラン・マイヤー曲線と多変量コックスモデルで生存率と再発率を評価する.

主要な成果

TERTp変異は,髄膜腫の4. 3%で発見されました.
TERTp変異性髄膜腫は,異質な分類と1pとCDKN2A/Bの喪失のような攻撃的な分子特性を示した.
単独のTERTp変異ではなく,CDKN2A/ Bの喪失が,全生存率と再発のない生存率に有意な影響を及ぼした.

結論

TERTp変異だけでは,最高級の髄膜腫を決定するには不十分です.
TERTシーケンシングは,他の分子マーカーと組み合わせると,高リスクのWHOグレード2の髄膜腫を特定することができます.
CDKN2A/Bの喪失は,TERTp変異性髄膜腫における攻撃的行動の決定的な要因である.