Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Clinical characteristics and registry-validated extended pedigrees of germline TP53 mutation carriers in Denmark

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Kinetics of the soluble urokinase plasminogen activator receptor (suPAR) in cirrhosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Exploring the hereditary background of renal cancer in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The Copenhagen Triage Algorithm is noninferior to a traditional triage algorithm: a cluster-randomized study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Detection of PMS2 Mutations by Screening Hereditary Nonpolyposis Colon Cancer Families from Denmark and Sweden

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Classmates motivate childhood cancer patients to participate in physical activity during treatment: A qualitative study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Psychotropic Medication Use in Parents of Children Diagnosed With Cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Exploring the hereditary background of renal cancer in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

INTRODUCTION: TP53 mutation carrier (Li-Fraumeni Syndrome, LFS) cohort studies often suffer from lack of extensive pedigree exploration.

METHODS: We performed a nation-wide exploration of TP53 mutation carrier families identified through all clinical genetics departments in Denmark. Pedigrees were expanded and verified using unique national person identification, cancer, cause of death, pathology, and church registries.

RESULTS: We identified 30 confirmed, six obligate and 14 assumed carriers in 15 families harboring 14 different mutations, including five novel and three de novo germline mutations. All but two (96%) developed cancer by age 54 years [mean debut age; 29.1 y., median 33.0 y., n = 26 (17F, 9M), range 1-54 y]]. Cancer was the primary cause of all deaths [average age at death; 34.5 years]. Two tumors were identified through registry data alone. Two independent families harbored novel c.80delC mutations shown to be related through an ancestor born in 1907. This exhaustive national collection yielded markedly fewer TP53 mutation carriers than the 300-1,100 expected based on estimated background population frequencies.

CONCLUSION: Germline TP53 mutations in Denmark are likely to be drastically underdiagnosed despite their severe phenotype. Following recent advances in surveillance options of LFS patients, lack of pre-symptomatic testing may lead to the mismanagement of some individuals.

OriginalsprogEngelsk
TidsskriftP L o S One
Vol/bind13
Udgave nummer1
Sider (fra-til)e0190050
ISSN1932-6203
DOI
StatusUdgivet - 2018

ID: 52408562