Biochemistry and Molecular Genetics Department, Hospital Clinic de Barcelona, Barcelona, Spain
Biomedicina, Universitat de Barcelona Facultat de Medicina i Ciencies de la Salut, Barcelona, Spain.
J Med Genet. 2024 Sep 24;61(10):939-942. doi: 10.1136/jmg-2024-110185.
It has long been observed that there are families in which non-medullary thyroid cancer (NMTC) occurs, but few syndromes and genes have been described to date. Proteins in the shelterin complex have been implied in cancer. Here, we have studied shelterin genes in families affected by NMTC (FNMTC).
We performed whole-exome sequencing (WES) in 10 affected individuals from four families with at least three affected members. Polymerase chain reaction (PCR) and Sanger sequencing were performed to search for variants in the gene in 40 FNMTC families. TINF2 transcripts and loss of heterozygosity (LOH) were studied in several affected patients of one family.
We found the c.507G>T variant in heterozygosis in the gene in one family, co-segregating in all five affected members. This variant affects the normal splicing. LOH was not observed.
Our results reinforce the gene as a susceptibility cause of FNMTC suggesting the importance of location of frameshift variants in . According to our data and previous literature, pathogenic variants appear to be a significant risk factor for the development of NMTC and/or melanoma.
长期以来，人们观察到有些家族会发生非髓样甲状腺癌（NMTC），但迄今为止，仅有少数综合征和基因被描述。庇护素复合物中的蛋白已被暗示与癌症有关。在这里，我们研究了受 NMTC（家族性非髓样甲状腺癌，FNMTC）影响的家族中的庇护素基因。
我们对来自四个至少有三个受影响成员的家族的 10 名受影响个体进行了全外显子组测序（WES）。对 40 个 FNMTC 家族进行了 PCR 和 Sanger 测序，以搜索 基因中的变异。在一个家族的几个受影响的患者中研究了 TINF2 转录物和杂合性丢失（LOH）。
我们在一个家族中发现了 基因中的杂合 c.507G>T 变异，该变异在所有五个受影响的成员中共同遗传。该变体影响正常剪接。未观察到 LOH。
我们的结果强化了 基因作为 FNMTC 的易感原因，表明移码变异的位置在 中很重要。根据我们的数据和以前的文献，致病性变异似乎是 NMTC 和/或黑色素瘤发展的重要危险因素。
