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The wide spectrum of POT1 gene variants correlates with multiple cancer types
- Source :
- Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, EUROPEAN JOURNAL OF HUMAN GENETICS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, European Journal of Human Genetics, European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (11), pp.1278-1281. ⟨10.1038/ejhg.2017.134⟩
- Publication Year :
- 2017
-
Abstract
- The POT1 protein binds and protects telomeres. Germline variants in the POT1 gene have recently been shown to be associated with risk of developing tumors in different tissues such as familial chronic lymphocytic leukemia, colorectal, glioma and melanoma tumors. Recently, we uncovered a variant in the POT1 gene (p.R117C) as causative of familial cardiac angiosarcomas (CAS) in Li-Fraumeni-like (LFL) syndrome families. Our in silico studies predicted that this protein had lost the ability to interact with TPP1 and single-stranded DNA. In vitro studies corroborated this prediction and showed that this lack of function leads to abnormally long telomeres. To better understand the POT1 gene and its role with tumorigenesis, we extended the study to LFL (with and without members affected with angiosarcomas (AS)) and sporadic AS and cardiac sarcomas. We found POT1 variants in the 20% of the families with members affected with AS and 10% of sporadic AS and sarcomas. In silico studies predicted that these new variants were damaging in the same manner as previously described for the POT1 p.R117C variants. The wide spectrum of variants in the POT1 gene leading to tumorigenesis in different tissues demonstrates its general importance. Study of the POT1 gene should be considered as routine diagnostic in these cancers.
- Subjects :
- 0301 basic medicine
Chronic lymphocytic leukemia
In silico
[SDV]Life Sciences [q-bio]
Hemangiosarcoma
Telomere-Binding Proteins
Short Report
Biology
medicine.disease_cause
Polymorphism, Single Nucleotide
Germline
Shelterin Complex
Heart Neoplasms
Li-Fraumeni Syndrome
03 medical and health sciences
Gene Frequency
Genetics
medicine
Humans
Gene
Allele frequency
Genetics (clinical)
ComputingMilieux_MISCELLANEOUS
Melanoma
medicine.disease
3. Good health
Telomere
030104 developmental biology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Carcinogenesis
Subjects
Details
- ISSN :
- 10184813 and 14765438
- Database :
- OpenAIRE
- Journal :
- Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, EUROPEAN JOURNAL OF HUMAN GENETICS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, European Journal of Human Genetics, European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (11), pp.1278-1281. ⟨10.1038/ejhg.2017.134⟩
- Accession number :
- edsair.doi.dedup.....ee45c670eb0fd1137b270d4d65023441