Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Pediatric Hematology/Oncology, King Abdullah Specialist Children's Hospital, Riyadh, Saudi Arabia.
Pediatr Blood Cancer. 2020 Jul;67(7):e28340. doi: 10.1002/pbc.28340. Epub 2020 May 2.
The frequency of pathogenic/likely pathogenic (P/LP) germline mutations in cancer-related genes among children with cancer in highly consanguineous populations is not well studied.
Whole-exome sequencing of germline DNA was performed in 60 children with acute leukemia. We used the St. Jude Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) data portal for the classification of germline variants by the St. Jude Medal Ceremony pipeline.
Fifty-seven patients had acute lymphoblastic leukemia (ALL) and three patients had acute myeloid leukemia. Parental consanguinity was present in 27 (45%) patients. All patients were of Arab ancestry. Three patients (5%) had a history of cancer in their siblings. Five patients (8.3%) had P/LP germline mutations in cancer-related genes. Three patients with B-ALL had heterozygous pathogenic mutations in TP53, BRCA1, and BRCA2; one patient with B-ALL had homozygous pathogenic mutation in PMS2; and one patient with T-ALL had LP homozygous mutation in AK2 that was associated with reticular dysgenesis. Among patients who had history of parental consanguinity, three (11%) had P/LP germline mutations compared with two (8%) in the absence of parental consanguinity. Fourteen (23%) patients had gold medal variants in cancer-related genes, 13 were heterozygous, and one was homozygous. Silver medal variants were present in 35 (58%) patients; all were heterozygous except one homozygous.
Children with acute leukemia in Saudi Arabia had low frequency of P/LP mutations in cancer-related genes despite the high rate of consanguinity. Larger studies using whole-genome sequencing are needed to further explore the heritability of childhood leukemia.
在高度近亲结婚的人群中，癌症相关基因中致病性/可能致病性（P/LP）种系突变在儿童癌症中的频率尚未得到很好的研究。
对 60 例急性白血病患儿的种系 DNA 进行外显子组测序。我们使用圣裘德儿科癌症变异致病性信息交流（PeCanPIE）数据门户，通过圣裘德奖章仪式管道对种系变异进行分类。
57 例患者患有急性淋巴细胞白血病（ALL），3 例患者患有急性髓系白血病。27 例（45%）患者存在父母近亲结婚。所有患者均为阿拉伯裔。3 例（5%）患者的兄弟姐妹有癌症病史。5 例（8.3%）患者在癌症相关基因中存在 P/LP 种系突变。3 例 B-ALL 患者携带 TP53、BRCA1 和 BRCA2 的杂合致病性突变；1 例 B-ALL 患者携带 PMS2 的纯合致病性突变；1 例 T-ALL 患者携带 AK2 的 LP 纯合突变，与网状发育不良有关。在有父母近亲结婚史的患者中，有 3 例（11%）存在 P/LP 种系突变，而无父母近亲结婚史的患者有 2 例（8%）。14 例（23%）患者在癌症相关基因中携带金质变体，其中 13 例为杂合子，1 例为纯合子。35 例（58%）患者存在银质变体；除 1 例纯合子外，均为杂合子。
尽管近亲结婚率较高，但在沙特阿拉伯的急性白血病患儿中，P/LP 基因突变在癌症相关基因中的频率较低。需要使用全基因组测序的更大规模研究来进一步探讨儿童白血病的遗传性。
