TY - JOUR

T1 - TINF2 is a major susceptibility gene in Danish patients with multiple primary melanoma

AU - Jensen, Marlene Richter

AU - Jelsig, Anne Marie

AU - Gerdes, Anne Marie

AU - Hölmich, Lisbet Rosenkrantz

AU - Kainu, Kati Hannele

AU - Lorentzen, Henrik Frank

AU - Hansen, Mary Højgaard

AU - Bak, Mads

AU - Johansson, Peter A.

AU - Hayward, Nicholas K.

AU - Van Overeem Hansen, Thomas

AU - Wadt, Karin A.W.

N1 - Publisher Copyright: © 2023

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - germline TINF2

KW - long telomeres

KW - multiple primary melanoma

U2 - 10.1016/j.xhgg.2023.100225

DO - 10.1016/j.xhgg.2023.100225

M3 - Journal article

C2 - 37646013

AN - SCOPUS:85168366931

VL - 4

JO - Human Genetics and Genomics Advances

JF - Human Genetics and Genomics Advances

SN - 2666-2477

IS - 4

M1 - 100225

ER -