Abdelghani Eman, Schieffer Kathleen M, Cottrell Catherine E, Audino Anthony, Zajo Kristin, Shah Nilay
Division of Hematology/Oncology/Blood and Marrow Transplantation, Nationwide Children's Hospital, Columbus, OH 43205, USA.
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43215, USA.
Cancers (Basel). 2023 Mar 8;15(6):1649. doi: 10.3390/cancers15061649.
Approximately 10% of pediatric malignancies are secondary to germline alterations in cancer-predisposing genes. Checkpoint kinase 2 () germline loss-of-function variants have been reported in pediatric cancer patients, but clinical phenotypes and outcomes are poorly described. We present our single-institution experience of pediatric oncology patients with germline alterations, including clinical presentations and outcomes.
Pediatric oncology patients with germline alterations were identified among those assessed by clinical or translational research at the Institute for Genomic Medicine at Nationwide Children's Hospital. A chart review of disease course was conducted on identified patients.
We identified 6 patients with germline variants from a cohort of 300 individuals, including 1 patient with concurrent presentation of Burkitt lymphoma and neuroblastoma, 3 patients with brain tumors, 1 patient with Ewing sarcoma, and 1 patient with myelodysplastic syndrome. Three patients had a family history of malignancies. Four patients were in remission; one was undergoing treatment; one patient had developed treatment-related meningiomas. We review prior data regarding variants in this population, challenges associated with variant interpretation, and genetic counseling for individuals with variants.
germline loss-of-function alterations occur in patients with a variety of pediatric tumors. Larger multicenter studies will improve our understanding of the incidence, phenotype, and molecular biology of germline variants in pediatric cancers.
约10%的儿童恶性肿瘤继发于癌症易感基因的种系改变。在儿童癌症患者中已报道了检查点激酶2（）种系功能丧失变异，但临床表型和预后描述甚少。我们介绍了我们单机构中患有种系改变的儿科肿瘤患者的情况，包括临床表现和预后。
在全国儿童医院基因组医学研究所接受临床或转化研究评估的患者中，识别出患有种系改变的儿科肿瘤患者。对已识别患者的疾病病程进行了病历回顾。
我们从300名个体队列中识别出6名患有种系变异的患者，包括1名同时患有伯基特淋巴瘤和神经母细胞瘤的患者、3名患有脑肿瘤的患者、1名患有尤因肉瘤的患者和1名患有骨髓增生异常综合征的患者。3名患者有恶性肿瘤家族史。4名患者处于缓解期；1名正在接受治疗；1名患者发生了与治疗相关的脑膜瘤。我们回顾了该人群中有关变异的数据、与变异解读相关的挑战以及对有变异个体的遗传咨询。
种系功能丧失改变发生在患有多种儿科肿瘤的患者中。更大规模的多中心研究将提高我们对儿童癌症中种系变异的发生率、表型和分子生物学的理解。
