Ridd Sarah, Peck Larissa, Bankar Aniket, Charames George S, Lerner-Ellis Jordan, Mahajan Radhika, Sabatini Peter J B, Wong Andrew, Malcolmson Janet, Kim Raymond H
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Sinai Health System, Toronto, ON, Canada.
NPJ Genom Med. 2025 May 15;10(1):39. doi: 10.1038/s41525-025-00476-6.
Genetic testing for solid tumor syndromes typically uses peripheral blood leukocytes (PBL) as the source of germline DNA. This approach has shortcomings in certain situations, such as somatic mosaicism and hematologic malignancies. Here we describe a case where germline genetic testing on PBL revealed an unsuspected diagnosis of myelodysplastic syndrome (MDS). A 68-year-old male with a history of three solid tumors and a significant family history of cancer underwent germline genetic testing with a 76-gene hereditary cancer panel. Initial testing using PBL revealed deletions of the entire APC and CTNNA1 genes, suggestive of a contiguous deletion of chromosome 5 (del(5q)). Subsequent testing on cultured fibroblasts was negative, indicating the deletions were somatic. Bone marrow analysis confirmed the presence of del(5q) and a diagnosis of MDS. This case demonstrates the potential to uncover hematologic disorders through hereditary cancer genetic testing, emphasizing the importance of careful results interpretation, multidisciplinary follow-up, and DNA source selection.
实体瘤综合征的基因检测通常使用外周血白细胞（PBL）作为种系DNA的来源。这种方法在某些情况下存在缺点，如体细胞镶嵌现象和血液系统恶性肿瘤。在此，我们描述了一例病例，对PBL进行的种系基因检测意外地揭示了骨髓增生异常综合征（MDS）的诊断。一名68岁男性，有三种实体瘤病史且有显著的癌症家族史，接受了一项包含76个基因的遗传性癌症检测板的种系基因检测。最初使用PBL进行的检测显示整个APC和CTNNA1基因缺失，提示5号染色体连续缺失（del(5q)）。随后对培养的成纤维细胞进行的检测为阴性，表明这些缺失是体细胞性的。骨髓分析证实存在del(5q)并诊断为MDS。该病例表明通过遗传性癌症基因检测有可能发现血液系统疾病，强调了仔细解读结果、多学科随访和选择DNA来源的重要性。
