Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany; DRESDEN-concept Genome Center, Technology Platform at the Center for Molecular and Cellular Bioengineering (CMCB), Technical University of Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.
Technical University of Munich, Germany, School of Medicine, Department of Pediatrics, Munich, Germany.
Genet Med. 2023 Aug;25(8):100875. doi: 10.1016/j.gim.2023.100875. Epub 2023 May 3.
Clinical checklists are the standard of care to determine whether a child with cancer shows indications for genetic testing. Nevertheless, the efficacy of these tests to reliably detect genetic cancer predisposition in children with cancer is still insufficiently investigated.
We assessed the validity of clinically recognizable signs to identify cancer predisposition by correlating a state-of-the-art clinical checklist to the corresponding exome sequencing analysis in an unselected single-center cohort of 139 child-parent data sets.
In total, one-third of patients had a clinical indication for genetic testing according to current recommendations, and 10.1% (14 of 139) of children harbored a cancer predisposition. Of these, 71.4% (10 of 14) were identified through the clinical checklist. In addition, >2 clinical findings in the checklist increased the likelihood to identifying genetic predisposition from 12.5% to 50%. Furthermore, our data revealed a high rate of genetic predisposition (40%, 4 of 10) in myelodysplastic syndrome cases, while no (likely) pathogenic variants were identified in the sarcoma and lymphoma group.
In summary, our data show high checklist sensitivity, particularly in identifying childhood cancer predisposition syndromes. Nevertheless, the checklist used here also missed 29% of children with a cancer predisposition, highlighting the drawbacks of sole clinical evaluation and underlining the need for routine germline sequencing in pediatric oncology.
临床检查表是确定癌症患儿是否需要进行基因检测的护理标准。然而，这些测试在可靠检测癌症患儿遗传易感性方面的效果仍未得到充分研究。
我们通过将最先进的临床检查表与未经选择的单中心 139 个患儿-父母数据集中的外显子组测序分析相关联，评估了临床可识别的特征来识别癌症易感性的有效性。
根据目前的建议，总共有三分之一的患者有进行基因检测的临床指征，10.1%（139 例中的 14 例）的儿童存在癌症易感性。其中，71.4%（14 例中的 10 例）通过临床检查表识别。此外，检查表中出现>2 个临床发现，将识别遗传易感性的可能性从 12.5%提高到 50%。此外，我们的数据显示，在骨髓增生异常综合征病例中，遗传易感性的发生率很高（40%，10 例中的 4 例），而在肉瘤和淋巴瘤组中未发现（可能）致病性变异。
总之，我们的数据表明检查表具有较高的敏感性，特别是在识别儿童癌症易感性综合征方面。然而，这里使用的检查表也错过了 29%具有癌症易感性的儿童，这突出了单纯临床评估的缺点，并强调了在儿科肿瘤学中常规进行种系测序的必要性。
