{
  "abstract": "Constitutional or germline pathogenic variants (GPVs) in protection of telomeres 1 (POT1) are associated with a variety of tumours resulting in the recognition of POT1-tumour predisposition syndrome (POT1-TPDS). These tumours may include cutaneous melanoma, angiosarcoma, haematological malignancy and brain tumours. Due to the rarity of POT1 GPVs and limited available data, the overall lifetime cancer risks for individuals with POT1-TPDS are unclear. Furthermore, there is scant evidence to support the role of surveillance in early cancer detection in this patient group. A recent international publication suggested a surveillance protocol similar to that used in Li-Fraumeni Syndrome (LFS) could be offered to POT1 pathogenic variant carriers, particularly where there are LFS-like features. However, current evidence for POT1-TPDS is not supportive of an equivalent lifetime cancer risk. Given the inclusion of POT1 in the National Test Directory in England and the need for UK-based guidance, an expert group undertook a literature review to assess the phenotypic spectrum of POT1-TPDS and to provide lifetime risk estimates of POT1-associated cancers. The available evidence was shared with a small working group of experts that included clinical geneticists, dermatologists, sarcoma specialists, haematologists and radiologists to cover all aspects of the cancers most commonly associated with POT1-TPDS. Following structured expert group discussions, we achieved consensus on best practice recommendations for a POT1-TPDS UK management protocol.",
  "authors": [
    {
      "affiliations": [
        "St George’s University of London, London, UK",
        "Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Olga Tsoulaki"
    },
    {
      "affiliations": [
        "Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK",
        "Manchester Centre for Genomic Medicine, Division of Evolution, Infection and Genomic sciences, The University of Manchester, Manchester, UK"
      ],
      "name": "D Gareth Evans"
    },
    {
      "affiliations": [
        "St John’s Institute of Dermatology, Guy's and St Thomas’ Hospitals NHS Trust, London, UK"
      ],
      "name": "Khushboo Sinha"
    },
    {
      "affiliations": [
        "Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK",
        "Department of Dermatology, NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, Newcastle upon Tyne, UK"
      ],
      "name": "Neil Rajan"
    },
    {
      "affiliations": [
        "St John’s Institute of Dermatology, Guy's and St Thomas’ Hospitals NHS Trust, London, UK"
      ],
      "name": "Farah Bakr"
    },
    {
      "affiliations": [
        "Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Helen Hatcher"
    },
    {
      "affiliations": [
        "Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, UK",
        "Clinical Studies, The Institute of Cancer Research, London, UK"
      ],
      "name": "Andrea Napolitano"
    },
    {
      "affiliations": [
        "Early Diagnosis and Detection Centre, Royal Marsden Hospital NHS Trust, London, England, UK"
      ],
      "name": "Elena Finn"
    },
    {
      "affiliations": [
        "Department of Haematology, The Royal Marsden NHS Foundation Trust, London, UK"
      ],
      "name": "Sunil Iyengar"
    },
    {
      "affiliations": [
        "Department of Radiology, Royal Marsden Hospital NHS Trust, London, UK"
      ],
      "name": "Aslam Sohaib"
    },
    {
      "affiliations": [
        "Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Timothy J Sadler"
    },
    {
      "affiliations": [
        "Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Claire Forde"
    },
    {
      "affiliations": [
        "Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK",
        "Manchester Centre for Genomic Medicine, Division of Evolution, Infection and Genomic sciences, The University of Manchester, Manchester, UK"
      ],
      "name": "Emma Roisin Woodward"
    },
    {
      "affiliations": [
        "Cancer Genetics Unit, Royal Marsden Hospital NHS Trust, London, UK"
      ],
      "name": "Terri P McVeigh"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK"
      ],
      "name": "Marc Tischkowitz"
    },
    {
      "affiliations": [
        "Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Fiona Lalloo"
    },
    {
      "affiliations": [
        "Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK",
        "Department of Clinical and Biomedical Sciences, University of Exeter Medical School, Exeter, UK"
      ],
      "name": "Helen Hanson"
    }
  ],
  "title": "UK clinical practice guidelines for the management of patients with constitutional POT1 pathogenic variants",
  "uid": "75720af2-73d9-56ed-93f6-162b336a53b1"
}