Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, University Medical Center Freiburg, University of Freiburg, Germany.
Department of Human Genetics, Hannover Medical School, Hannover, Germany.
Eur J Med Genet. 2023 May;66(5):104718. doi: 10.1016/j.ejmg.2023.104718. Epub 2023 Feb 9.
Soft tissue sarcomas (STS) may arise as a consequence of germline variants in cancer predisposition genes (CPGs). We believe that elucidating germline sarcoma predisposition is critical for understanding disease biology and therapeutic requirements. Participation in surveillance programs may allow for early tumor detection, early initiation of therapy and, ultimately, better outcomes. Among children, adolescents, and adults diagnosed with soft-tissue sarcomas and examined as part of published germline sequencing studies, pathogenic/likely pathogenic (P/LP) variants in CPGs were reported in 7-33% of patients. P/LP germline variants were detected most frequently in TP53, NF1 and BRCA1/2. In this review, we describe reported associations between soft tissue sarcomas and germline variants in CPGs, with mentioning of locally aggressive and benign soft tissue tumors that have important associations with cancer predisposition syndromes. We also discuss recommendations for diagnostic germline genetic testing. Testing for sarcoma-predisposing germline variants should be considered as part of the routine clinical workup and care of any child, adolescent, or adult diagnosed with STS and take into account consequences for the whole family.
软组织肉瘤 (STS) 可能是由于癌症易感基因 (CPG) 的种系变异引起的。我们认为，阐明种系肉瘤易感性对于了解疾病生物学和治疗需求至关重要。参与监测计划可能有助于早期发现肿瘤，早期开始治疗，最终获得更好的结果。在作为已发表的种系测序研究的一部分进行检查的被诊断患有软组织肉瘤的儿童、青少年和成年人中，7-33%的患者报告存在 CPG 中的致病性/可能致病性 (P/LP) 变异。最常检测到 P/LP 种系变异的基因是 TP53、NF1 和 BRCA1/2。在这篇综述中，我们描述了软组织肉瘤与 CPG 中的种系变异之间的报告关联，并提到了与癌症易感性综合征有重要关联的局部侵袭性和良性软组织肿瘤。我们还讨论了种系遗传检测的建议。应考虑对任何被诊断患有 STS 的儿童、青少年或成年人进行致瘤性种系变异检测，作为常规临床评估和护理的一部分，并考虑对整个家庭的影响。
