ArticleNature genetics2014
Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00339222 (Family Study of Melanoma in Italy), which is not on this map. Cited by 203 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
203citing papers in PubMed, 6 pooled it
19.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Family Study of Melanoma in Italy
Who cites it
203 citing papers in PubMed, 6 syntheses or guidelines pooled it, 324 citations in OpenAlex.
- UK clinical practice guidelines for the management of patients with constitutionalJournal of medical genetics · 2025Guideline
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.Nature genetics · 2020Pooled it
- Combining common genetic variants and non-genetic risk factors to predict risk of cutaneous melanoma.Human molecular genetics · 2018Pooled it
- Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.Nature genetics · 2015Pooled it
- DCAF4, a novel gene associated with leucocyte telomere length.Journal of medical genetics · 2015Pooled it
- Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family.Human genetics · 2015Trial
- How telomere attrition protects against cancer.Nature reviews. Genetics · 2026Review
- Telomere length of both parents contributes to heritable POT1 cancer-predisposition syndrome.Nature communications · 2026Article
- Disruption of CTCF binding by germline non-coding variants inmedRxiv : the preprint server for health sciences · 2026Article
- A high-penetrance intergenic variant at 9p21 confers melanoma susceptibility.Research square · 2026Article
- Article
- Clonal Signatures of Telomere Biology Disorders.Current hematologic malignancy reports · 2026Review
- Telomere length of both parents contribute to heritable POT1 cancer-predisposition syndrome.bioRxiv : the preprint server for biology · 2026Article
- Rare Germline Variants in CDKN2A-Negative Children and Adolescents With Cutaneous Melanoma.Pigment cell & melanoma research · 2026Article
- GermlineGenetics in medicine open · 2026Article
- Whole exome sequencing identified two novel mutations ofFrontiers in cell and developmental biology · 2026Article
- Mice carrying the homologous human shelterin POT1-L259S mutation linked to pulmonary fibrosis show a telomerase deficiency-like phenotype with telomere shortening with increasing mouse generations.Genes & development · 2025Article
- POT1 genetic testing in melanoma-prone families in Sweden: germline variant prevalence and tumor spectrum in identified carriers.Acta oncologica (Stockholm, Sweden) · 2025Article
- Genetic Landscape of Familial Melanoma.Genes · 2025Review
143 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
52 authors at 16 institutions in 5 countries.
Jianxin Shi1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2].
Xiaohong R Yang1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2].
Bari BallewDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Melissa RotunnoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Donato CalistaDepartment of Dermatology, Maurizio Bufalini Hospital, Cesena, Italy.
Maria Concetta FargnoliDepartment of Dermatology, University of L'Aquila, L'Aquila, Italy.
Paola Ghiorzo1] Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy. [2] Genetics of Rare Hereditary Cancers, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Brigitte Bressac-de PailleretsService de Génétique, Gustave Roussy, Villejuif, France.
Eduardo Nagore1] Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain. [2] Department of Dermatology, Universidad Católica de Valencia, Valencia, Spain.
Marie Francoise AvrilUniversité Paris Descartes, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, Paris, France.
Neil E CaporasoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Mary L McMasterDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Michael Cullen1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick, Inc., Frederick, Maryland, USA.
Zhaoming Wang1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick, Inc., Frederick, Maryland, USA.
Xijun Zhang1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick, Inc., Frederick, Maryland, USA.
NCI DCEG Cancer Sequencing Working Group
NCI DCEG Cancer Genomics Research Laboratory
French Familial Melanoma Study Group
William Bruno1] Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy. [2] Genetics of Rare Hereditary Cancers, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Lorenza Pastorino1] Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy. [2] Genetics of Rare Hereditary Cancers, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Paola QueiroloGenetics of Rare Hereditary Cancers, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Jose Banuls-RocaDepartment of Dermatology, Hospital General Universitario de Alicante, Alicante, Spain.
Zaida Garcia-CasadoLaboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain.
Amaury Vaysse1] INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France. [2] Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
Hamida Mohamdi1] INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France. [2] Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
Yasser Riazalhosseini1] McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Mario FoglioSAS Quantome, Paris, France.
Fanélie JouenneService de Génétique, Gustave Roussy, Villejuif, France.
Xing HuaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Paula L HylandDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Jinhu YinLaboratory of Molecular Gerontology, National Institute on Aging, US National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland, USA.
Haritha VallabhaneniLaboratory of Molecular Gerontology, National Institute on Aging, US National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland, USA.
Weihang ChaiSection of Medical Sciences, School of Molecular Biosciences, Washington State University, Spokane, Washington, USA.
Paola MinghettiDepartment of Dermatology, Maurizio Bufalini Hospital, Cesena, Italy.
Cristina PellegriniDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Sarangan RavichandranSAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Simulation, Analysis and Mathematical Modeling Group, Advanced Biomedical Computing Center, Frederick, Maryland, USA.
Alexander Eggermont1] Service de Génétique, Gustave Roussy, Villejuif, France. [2] Université Paris-Sud, Kremlin Bicêtre France, Gustave Roussy, Villejuif, France.
Mark Lathrop1] McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [3] Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France.
Ketty PerisDepartment of Dermatology, University of L'Aquila, L'Aquila, Italy.
Giovanna Bianchi ScarraDepartment of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
Giorgio LandiDepartment of Dermatology, Maurizio Bufalini Hospital, Cesena, Italy.
Sharon A SavageDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Joshua N SampsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Ji He1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick, Inc., Frederick, Maryland, USA.
Meredith Yeager1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick, Inc., Frederick, Maryland, USA.
Lynn R GoldinDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Florence Demenais1] INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France. [2] Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.ORCID 0000000183610936
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Margaret A TuckerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Alisa M GoldsteinDivision of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Yie LiuLaboratory of Molecular Gerontology, National Institute on Aging, US National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland, USA.
Maria Teresa Landi1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. [2].
National Institutes of Health · USInserm · FROspedale “M. Bufalini” di Cesena · ITUniversity of L'Aquila · ITDepartment of Health and Human Services · USFrederick National Laboratory for Cancer Research · USFundación Instituto Valenciano de Oncología · ESWashington State University Spokane · USDélégation Paris 5 · FRFondation Jean Dausset-CEPH · FRHospital General Universitario de Alicante Doctor Balmis · ESInstitut Gustave Roussy · FRIstituti di Ricovero e Cura a Carattere Scientifico · ITNational Institute on Aging · USUniversité Paris Cité · FRUniversité Paris-Sud · FR
Funding
Family Studies ZIACP004410 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI SAVAGE, SHARON A. · 2009 to 2025
$56.1MSTUDIES OF PERSONS AT HIGH RISK OF CANCER--GENETIC EPIDEMIOLOGYZ01CP004410 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI TUCKER, MARGARET · 1985 to 2008
$15.0MThe role of DNA damage and repair at telomeresZIAAG000744 · NIA · NATIONAL INSTITUTE ON AGING · PI LIU, YIE · 2009 to 2016
$3.9MCCR NIH HHS HHSN261200800001CIntramural NIH HHS Z01 CP004410NCI NIH HHS HHSN261200800001E
Abstract
Although CDKN2A is the most frequent high-risk melanoma susceptibility gene, the underlying genetic factors for most melanoma-prone families remain unknown. Using whole-exome sequencing, we identified a rare variant that arose as a founder mutation in the telomere shelterin gene POT1 (chromosome 7, g.124493086C>T; p.Ser270Asn) in five unrelated melanoma-prone families from Romagna, Italy. Carriers of this variant had increased telomere lengths and numbers of fragile telomeres, suggesting that this variant perturbs telomere maintenance. Two additional rare POT1 variants were identified in all cases sequenced in two separate Italian families, one variant per family, yielding a frequency for POT1 variants comparable to that for CDKN2A mutations in this population. These variants were not found in public databases or in 2,038 genotyped Italian controls. We also identified two rare recurrent POT1 variants in US and French familial melanoma cases. Our findings suggest that POT1 is a major susceptibility gene for familial melanoma in several populations.
Indexed as
Models, MolecularAmino Acid SequenceBase SequenceComputational BiologyCutaneous Malignant MelanomaExomeFranceGenetic Predisposition to DiseaseHumansIn Situ Hybridization, FluorescenceItalyMelanomaMolecular Sequence DataMutation, MissenseNeoplasms, Connective TissuePedigreePOT1 protein, humanShelterin ComplexTelomere-Binding Proteins
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Registered trials
NCT00339222ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.