Lack of Mutations in POT1 Gene in Selected Families with Familial Non-Medullary Thyroid Cancer

Orois, Aida; Badenas, Cèlia; Reverter, Jordi L.; López, Verónica; Potrony, Míriam; Mora, Mireia; Halperín, Irene; Oriola, Josep

doi:10.1007/s12672-020-00383-5

Cited by 14 publications

(8 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Germline deleterious mutations in POT1 have previously been associated with susceptibility to melanoma [9,10], glioma [13], colorectal cancer [16], Li-Fraumeni-like syndrome [14], and chronic lymphocytic leukemia [16]. Orois et al analyzed seven FNMTC families with the sole aim of identifying POT1 mutations but were unable to detect any variants in these families [27]. It is of particular interest to note that predicting the phenotype simply by attaining the genotype is not possible.…”

Section: Discussionmentioning

confidence: 99%

A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer

Srivastava

Miao

Skopelitou

et al. 2020

Cancers

View full text Add to dashboard Cite

Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole-genome sequencing study of five families with occurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we report in silico analyses and in vitro experiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of the Protection of Telomeres 1 (POT1) gene in one of the families. The results showed a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293T cells carrying POT1 p.V29L showed increased telomere length in comparison to wild-type cells, suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. While one germline mutation in POT1 has already been reported in a melanoma-prone family with prevalence of thyroid cancers, we report the first of such mutations in a family affected solely by NMTCs, thus expanding current knowledge on shelterin complex-associated cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer

Srivastava

Miao

Skopelitou

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Loss-of-function or reduced activity of POT1 seems to play a pathogenetic role via dysregulation of telomere protection [68]. However, a lack of mutations in the POT1 gene in selected families with NSFNMTC, with at least three affected members, has been reported in another recent study [102].…”

Section: Genetic Featuresmentioning

confidence: 97%

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

et al. 2021

View full text Add to dashboard Cite

Cancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past decade. However the incidence of familial disease has not been emphasized and is often overlooked in routine practice. A careful clinical documentation of family history or familial syndromes that can be associated with thyroid disease can help identify germline susceptibility-driven thyroid neoplasia. In this review, we summarize a large body of information about both syndromic and non-syndromic familial thyroid carcinomas. A significant number of patients with inherited non-medullary thyroid carcinomas manifest disease that appears to be sporadic disease even in some syndromic cases. The cytomorphology of the tumor(s), molecular immunohistochemistry, the findings in the non-tumorous thyroid parenchyma and other associated lesions may provide insight into the underlying syndromic disorder. However, the increasing evidence of familial predisposition to non-syndromic thyroid cancers is raising questions about the importance of genetics and epigenetics. What appears to be “sporadic” is becoming less often truly so and more often an opportunity to identify and understand novel genetic variants that underlie tumorigenesis. Pathologists must be aware of the unusual morphologic features that should prompt germline screening. Therefore, recognition of harbingers of specific germline susceptibility syndromes can assist in providing information to facilitate early detection to prevent aggressive disease.

show abstract

“…These results suggest that intronic variation in POT1 may affect key protein-binding interactions that affect telomere maintenance and genomic integrity ( 15 ). Another recent study, however, including 4 Spanish families with familial PTC, did not detect potentially pathogenic germline mutations in POT1 by WES, thus minimizing the possible role of this gene in NS-FNMTC ( 61 ).…”

Section: Susceptibility Genes Associated With Ns-fnmtcmentioning

confidence: 91%

Susceptibility Genes and Chromosomal Regions Associated With Non-Syndromic Familial Non-Medullary Thyroid Carcinoma: Some Pathogenetic and Diagnostic Keys

et al. 2022

View full text Add to dashboard Cite

Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic alterations involved in the pathogenesis of sporadic follicular cell derived tumors are well recognized, while the predisposing alterations implicated in hereditary follicular tumors are less well known. Since the genetic background of syndromic familial non-medullary carcinoma has been well established, here we review the pathogenesis of non-syndromic familial non-medullary carcinoma emphasizing those aspects that may be useful in clinical and pathological diagnosis. Non-syndromic familial non-medullary carcinoma has a complex and heterogeneous genetic basis involving several genes and loci with a monogenic or polygenic inheritance model. Most cases are papillary thyroid carcinoma (classic and follicular variant), usually accompanied by benign thyroid nodules (follicular thyroid adenoma and/or multinodular goiter). The possible diagnostic and prognostic usefulness of the changes in the expression and/or translocation of various proteins secondary to several mutations reported in this setting requires further confirmation. Given that non-syndromic familial non-medullary carcinoma and sporadic non-medullary thyroid carcinoma share the same morphology and somatic mutations, the same targeted therapies could be used at present, if necessary, until more specific targeted treatments become available.

show abstract

Lack of Mutations in POT1 Gene in Selected Families with Familial Non-Medullary Thyroid Cancer

Cited by 14 publications

References 32 publications

A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer

A Germline Mutation in the POT1 Gene Is a Candidate for Familial Non-Medullary Thyroid Cancer

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

Susceptibility Genes and Chromosomal Regions Associated With Non-Syndromic Familial Non-Medullary Thyroid Carcinoma: Some Pathogenetic and Diagnostic Keys

Contact Info

Product

Resources

About