Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Genet Med. 2022 Nov;24(11):2367-2379. doi: 10.1016/j.gim.2022.08.010. Epub 2022 Sep 16.
As research on hereditary hematologic malignancy syndromes (HHMS) are accumulating, cancer genetics clinics are identifying more adult hematology patients with an inherited component to their disease. However, investigations for HHMS are complex, and there is no formal consensus on genetic testing criteria.
We developed genetic testing criteria for adult hematology patients through a comprehensive literature review and our experience at the Princess Margaret Cancer Centre. We validated our criteria by applying them retrospectively to patients referred to our clinic for HHMS assessment.
Our genetic testing criteria are comprehensive of myeloid malignancies, lymphoid malignancies, and bone marrow failure, including age at diagnosis, family history, and genetic test results in blood and bone marrow. Of the 104 patients who met the criteria, 26% had at least 1 actionable variant in any gene associated with an increased risk of cancer and 13% had an actionable variant resulting in an HHMS diagnosis. A total of 15 patients had incidental findings, including 11 patients with a pathogenic variant associated with carrier status for an autosomal recessive disorder and 4 patients with a mosaic result.
Our high gene positivity rate shows the utility of a broad approach to germline testing in an adult hematology population.
随着遗传性血液恶性肿瘤综合征（HHMS）研究的积累，癌症遗传学诊所发现越来越多的成年血液系统疾病患者存在疾病的遗传成分。然而，HHMS 的调查非常复杂，并且在遗传检测标准方面没有正式的共识。
我们通过全面的文献回顾和在玛格丽特公主癌症中心的经验，为成年血液系统疾病患者制定了遗传检测标准。我们通过将这些标准应用于我们诊所进行 HHMS 评估的患者进行回顾性验证。
我们的遗传检测标准全面涵盖了髓系恶性肿瘤、淋巴恶性肿瘤和骨髓衰竭，包括诊断时的年龄、家族史以及血液和骨髓中的遗传检测结果。在符合标准的 104 名患者中，26%的患者在任何与癌症风险增加相关的基因中至少有 1 个可操作的变异，13%的患者有可操作的变异导致 HHMS 诊断。共有 15 名患者存在偶发发现，包括 11 名患者携带常染色体隐性疾病的致病性变异和 4 名患者存在嵌合体结果。
我们的高基因阳性率表明在成年血液系统疾病患者中广泛进行种系检测的有效性。
