PDF(Pubmed)
Abstract：
UNASSIGNED: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma.
UNASSIGNED: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected.
UNASSIGNED: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH, and CHEK2 were most common (3/15, 20% each). BRCA1 variants occurred in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Prior cancer diagnosis was found in 5/15 patients (33%). Second-hit somatic variants were seen in 3/15 patients (20%) in NF1, MUTYH, and MSH2. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. 14/15 (93%) of patients discovered their pathogenic variant as a result of their paired glioma sequencing.
UNASSIGNED: These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further studies that can determine the role of variants in gliomagenesis and confirm the occurrence and types of pathogenic germline variants in patients with IDH wild type compared to IDH mutant tumors are necessary.
UNASSIGNED: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected.
UNASSIGNED: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH, and CHEK2 were most common (3/15, 20% each). BRCA1 variants occurred in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Prior cancer diagnosis was found in 5/15 patients (33%). Second-hit somatic variants were seen in 3/15 patients (20%) in NF1, MUTYH, and MSH2. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. 14/15 (93%) of patients discovered their pathogenic variant as a result of their paired glioma sequencing.
UNASSIGNED: These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further studies that can determine the role of variants in gliomagenesis and confirm the occurrence and types of pathogenic germline variants in patients with IDH wild type compared to IDH mutant tumors are necessary.
摘要：
■目前没有针对神经胶质瘤患者的一致生殖系测试指南，所以种系致病变异的流行仍然未知。这项研究旨在确定成人神经胶质瘤中致病种系变异的患病率和类型。
■从2018年8月至2022年4月对具有配对肿瘤/正常测序的单个机构进行了回顾性审查，并收集了相应的临床数据。
■我们确定了152例胶质瘤患者，其中15例（9.8％）具有致病性种系变异。恶性种系变异见于11/84(13.1%)胶质母细胞瘤,IDH野生型；3/42（7.1%）星形细胞瘤，IDH突变体；少突胶质细胞瘤的1/26（3.8％），IDH突变体,和1p/19q共同删除的患者。BRCA2、MUTYH、CHEK2最常见（3/15，各20%）。BRCA1变异发生在2/15（13%）患者中，NF1，ATM，MSH2和MSH3分别发生在一名患者中（7％）。在5/15患者中发现了先前的癌症诊断（33％）。在NF1、MUTYH、和MSH2。在6/15（40％）具有致病性种系变异的患者中进行了遗传学转诊。14/15（93％）的患者由于配对的神经胶质瘤测序而发现了致病变异。
■这些研究结果表明，在确定遗传性癌症综合征时可能存在一个被忽视的机会，对监测以及潜在的更广泛的治疗方案有影响。需要进一步的研究，可以确定变体在神经胶质瘤形成中的作用，并确认与IDH突变肿瘤相比，IDH野生型患者中致病性种系变体的发生和类型。
■从2018年8月至2022年4月对具有配对肿瘤/正常测序的单个机构进行了回顾性审查，并收集了相应的临床数据。
■我们确定了152例胶质瘤患者，其中15例（9.8％）具有致病性种系变异。恶性种系变异见于11/84(13.1%)胶质母细胞瘤,IDH野生型；3/42（7.1%）星形细胞瘤，IDH突变体；少突胶质细胞瘤的1/26（3.8％），IDH突变体,和1p/19q共同删除的患者。BRCA2、MUTYH、CHEK2最常见（3/15，各20%）。BRCA1变异发生在2/15（13%）患者中，NF1，ATM，MSH2和MSH3分别发生在一名患者中（7％）。在5/15患者中发现了先前的癌症诊断（33％）。在NF1、MUTYH、和MSH2。在6/15（40％）具有致病性种系变异的患者中进行了遗传学转诊。14/15（93％）的患者由于配对的神经胶质瘤测序而发现了致病变异。
■这些研究结果表明，在确定遗传性癌症综合征时可能存在一个被忽视的机会，对监测以及潜在的更广泛的治疗方案有影响。需要进一步的研究，可以确定变体在神经胶质瘤形成中的作用，并确认与IDH突变肿瘤相比，IDH野生型患者中致病性种系变体的发生和类型。
