Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.
Department of Plastic and Reconstructive Surgery, Herlev and Gentofte Hospital, 2730 Herlev, Denmark.
HGG Adv. 2023 Jul 23;4(4):100225. doi: 10.1016/j.xhgg.2023.100225. eCollection 2023 Oct 12.
encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline variants in that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added to the genes, together with other telomere maintenance genes such as , , , and . We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in (p.(Arg265Ter)) was identified in four unrelated participants. The telomere lengths of three variant carriers were >90% percentile. In a routine diagnostic setting, the variant was identified in two more families, including an additional MPM patient and monozygotic twins with thyroid cancer and other cancer types. A total of 10 individuals from six independent families were confirmed carriers, all with cancer history, predominantly melanoma. Our findings suggest a major role of in Danish patients with MPM. In addition to melanoma, other cancers in the six families include thyroid, renal, breast, and sarcoma, supporting a CPS in which melanoma, thyroid cancer, and sarcoma predominate. Further studies are needed to establish the full spectrum of associated cancer types and characterize lifetime cancer risk in carriers.
编码 TINF2 蛋白，该蛋白是端粒调节中庇护体复合物的一个亚基。最近的三项研究将 6 种截短的种系变体与先前与端粒延长引起的癌症易感性综合征 (CPS) 相关联。这增加了 基因，以及其他端粒维持基因，如 、 、 和 。我们报告了一项对 102 名丹麦多发性原发性黑色素瘤 (MPM) 患者的临床研究，其中 4 名无亲缘关系的参与者中发现了种系截短变体 (p.(Arg265Ter))。三个变异携带者的端粒长度 >90%百分位。在常规诊断环境中，在另外两个家族中发现了该变体，包括另外一名 MPM 患者和患有甲状腺癌和其他癌症类型的同卵双胞胎。共有来自六个独立家庭的 10 名个体被确认为携带者，他们都有癌症病史，主要是黑色素瘤。我们的研究结果表明， 在丹麦 MPM 患者中起主要作用。除了黑色素瘤，六个家庭中的其他癌症包括甲状腺癌、肾癌、乳腺癌和肉瘤，支持黑色素瘤、甲状腺癌和肉瘤为主的 CPS。需要进一步研究来确定相关癌症类型的全貌，并描述携带者的终生癌症风险。
