TINF2编码TINF2蛋白，该蛋白是shelterin复合物中的一个子单位，对端粒调控至关重要。最近的三项研究发现了六个TINF2中截断的生殖系变异体，这些变异体以前已与由端粒长度延长引起的癌症易感综合征（CPS）相关联。这将TINF2与其他端粒维持基因（如ACD、POT1、TERF2IP和TERT）一起归属于长端粒综合征基因。我们报告了对102名丹麦多原发黑色素瘤（MPM）患者的临床研究，其中发现了四个无关参与者中TINF2中截断的生殖系变异体（p.(Arg265Ter)）。三个变异体携带者的端粒长度大于90%的百分位数。在常规诊断中，该变异体在另外两个家庭中被发现，包括一个额外的MPM患者和一对单卵双生子，他们患有甲状腺癌和其他癌症类型。共有来自六个独立家庭的十个个体被证实为携带者，其中所有人都有癌症病史，主要是黑色素瘤。我们的发现表明，在丹麦MPM患者中，TINF2起着重要的作用。除了黑色素瘤外，在这六个家庭中还涉及了甲状腺、肾脏、乳腺和肉瘤等其他癌症，支持了一种以黑色素瘤、甲状腺癌和肉瘤为主导的CPS。需要进一步的研究来确定相关癌症类型的完整谱系，并对携带者的终身癌症风险进行特征化。© 2023.

TINF2 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 TINF2 that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added TINF2 to the long telomere syndrome genes, together with other telomere maintenance genes such as ACD, POT1, TERF2IP, and TERT. We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in TINF2 (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 TINF2 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.© 2023.