NEW YORK – Glioma brain tumors found in adolescent and young adult patients may fall into higher- or lower-risk subgroups depending on features such as tumor grade and the presence or absence of certain alterations, according to new research from an international team led by Canadian investigators.

纽约——根据加拿大研究人员领导的国际团队的新研究，青少年和年轻成人患者中发现的胶质瘤脑肿瘤可能根据肿瘤等级和某些特定变化的存在与否等特征，分为高风险或低风险亚组。

Their findings,

他们的发现，

published

已发布

in

在

Nature Cancer

自然癌症

on Wednesday, '

周三，'

give insight into the origins of these tumors and offer opportunities for novel treatment strategies aimed at altering the natural behavior of these gliomas, called 'cancer interception,''

深入了解这些肿瘤的起源，并为旨在改变这些胶质瘤自然行为的新型治疗策略提供机会，这种策略被称为“癌症干预”。

Julie Bennett, a physician and neuro-oncology researcher with the Hospital for Sick Children (SickKids) and the Princess Margaret Cancer Centre, who co-leads the Canadian Adolescent and Young Adult Neuro-Oncology Network, said in an email.

茱莉·贝内特是一位医生，也是多伦多病童医院（SickKids）和玛格丽特公主癌症中心的神经肿瘤学研究员，她共同领导加拿大青少年和年轻成人神经肿瘤网络，在一封电子邮件中说道。

For their study, Bennett and her colleagues generated droplet digital PCR, targeted panel sequencing, and array-based methylation profiling data on tumor samples from up to 1,456 glioma patients. In addition, they brought in clinical data and copy number variants (CNV) gleaned from whole-genome sequencing of tumor samples and matched normal blood samples from a subset of 37 mismatch repair-proficient patients..

在他们的研究中，Bennett 和她的同事对来自多达 1,456 名胶质瘤患者的肿瘤样本进行了液滴数字 PCR、靶向面板测序和基于阵列的甲基化分析数据的生成。此外，他们还引入了临床数据和拷贝数变异 (CNV)，这些数据是从 37 名错配修复功能正常患者的肿瘤样本和匹配的正常血液样本的全基因组测序中收集的。

The study participants ranged in age from infancy to 39 years and were treated at Toronto hospitals between early 2000 and mid-2019, though the analyses largely centered on gliomas found in 873 patients between the ages of 15 and 39.

研究参与者年龄范围从婴儿期到39岁不等，他们在2000年初至2019年中期于多伦多的医院接受治疗，尽管分析主要集中于873名15至39岁患者中发现的胶质瘤。

While past studies uncovered distinctive pediatric-glioma and adult-glioma alterations that can inform treatment and prognosis, molecular changes affecting the biology, location, treatment response, and prognostic outlook for adolescents or young adults with glioma have been less fully investigated..

过去的研究揭示了儿童胶质瘤和成人胶质瘤的不同变化，这些变化可以为治疗和预后提供信息，但对青少年或年轻成人胶质瘤患者的生物学、位置、治疗反应和预后展望产生影响的分子变化尚未得到充分研究。

'There have not been any large studies focused on the molecular characteristics of the [adolescent and young adult glioma] population in the past,' Bennett noted.

“过去没有任何大型研究关注[青少年和年轻成人胶质瘤]人群的分子特征，”贝内特指出。

With their multiomic analyses, the investigators saw extensive heterogeneity for adolescent and young adult gliomas, which ranged from tumors with features that resembled pediatric glioma cases to tumors with adult-type glioma features. Nearly one-third of tumors were enriched for alterations implicated in pediatric glioma cases, for example..

通过多组学分析，研究人员观察到青少年和年轻成人胶质瘤的广泛异质性，这些肿瘤的特征范围从类似于儿童胶质瘤病例的肿瘤到具有成人型胶质瘤特征的肿瘤不等。例如，近三分之一的肿瘤富集了与儿童胶质瘤病例相关的改变。

The investigators also saw signs that the low-grade gliomas found in adolescent and young adult patients often showed up in different locations in the brain compared to low-grade gliomas found in children, consistent with distinct cellular origins.

研究人员还发现，青少年和年轻成人患者中的低级别胶质瘤常常与儿童中的低级别胶质瘤出现在大脑的不同位置，这与不同的细胞起源一致。

They noted that individuals with low-grade tumors and pediatric glioma-like alterations tended to have better progression-free survival and overall outcomes relative to cases involving adult-type glioma alterations, suggesting targeted treatment options with reduced toxicity in some low-risk adolescent or young adult cases..

他们指出，与涉及成人型胶质瘤改变的病例相比，具有低级别肿瘤和儿童胶质瘤样改变的个体往往有更好的无进展生存期和总体预后，这表明在一些低风险的青少年或年轻成人病例中可能存在降低毒性的靶向治疗选择。

Even so, the team highlighted a set of adolescent or young adult tumors that appeared to be particularly prone to becoming more aggressive high-grade glioma tumors as patients age, including tumors containing the BRAF p.V600E mutation, mutant IDH, or alterations involving the FGFR gene.

即便如此，该团队强调了一组青少年或年轻成人的肿瘤，这些肿瘤随着患者年龄增长似乎特别容易发展为更具侵袭性的高级别胶质瘤肿瘤，其中包括含有BRAF p.V600E突变、IDH突变或涉及FGFR基因改变的肿瘤。

Based on these and other results, the author suggested that additional research may lead to combination treatments for improving outcomes in patients with high-grade tumors and called for clinical efforts aimed at recognizing pediatric glioma-like tumors in the adolescent and young adult patient group..

基于这些和其他结果，作者建议，额外的研究可能会带来改善高级别肿瘤患者的治疗效果的联合治疗方法，并呼吁在临床工作中针对青少年和年轻患者群体识别出类似小儿胶质瘤的肿瘤。

'These findings demonstrate unique vulnerabilities and differences in tumor behavior based on age at diagnosis and cell of origin,' the authors wrote. 'Further work is needed to detect tumors and intervene at earlier stages of tumorigenesis to prevent malignant transformation, with the potential to alter the natural history of these tumors.'.

“这些研究结果展示了基于诊断年龄和细胞起源的肿瘤行为的独特脆弱性和差异，”作者写道。“还需要进一步的工作来检测肿瘤，并在肿瘤发生的早期阶段进行干预，以防止恶性转化，这有可能改变这些肿瘤的自然病程。”