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 -