The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI:10.1101/mcs.a006275

Majd Al Assaad, Gunes Gundem, Benjamin Liechty, Andrea Sboner, Juan Medina, Elli Papaemmanuil, Cora N Sternberg, Asher Marks, Mark M Souweidane, Jeffrey P Greenfield, Ivy Tran, Matija Snuderl, Olivier Elemento, Marcin Imielinski, David J Pisapia, Juan Miguel Mosquera

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引用次数: 0

Abstract

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

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升级分子诊断在低级别儿童癌症患者中的重要性。

毛细胞星形细胞瘤是最常见的儿童脑肿瘤，通常表现为低度肿瘤。我们报告两例毛细胞星形细胞瘤伴非典型肿瘤进展。病例1涉及一名12岁男孩，患有无法切除的鞍上肿瘤，BRAF重排阴性，但携带BRAF p.V600E突变。他经历了肿瘤大小的缩小和稳定的疾病后达非尼治疗。病例2描述了一名患有丘脑肿瘤的6岁男孩，该男孩接受了多次切除，但使用靶向下一代测序（NGS）未检测到可操作的驱动因素。全基因组和RNAseq分析确定了FGFR1和RAS通路激活中的内部串联重复。未来的管理选择包括FGFR1抑制剂。这些病例证明了升级癌症儿童脑分子诊断的重要性，提倡在靶向小组没有信息的情况下，早期反射到整合的全基因组测序和转录组分析。识别分子驱动因素可以显著影响治疗决策并改善患者预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.