Journal of Hematology & Oncology (Aug 2022)
Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry
- Judith Penkert,
- Farina J. Strüwe,
- Christina M. Dutzmann,
- Beate B. Doergeloh,
- Emilie Montellier,
- Claire Freycon,
- Myriam Keymling,
- Heinz-Peter Schlemmer,
- Birte Sänger,
- Beatrice Hoffmann,
- Tanja Gerasimov,
- Claudia Blattmann,
- Sebastian Fetscher,
- Michael Frühwald,
- Simone Hettmer,
- Uwe Kordes,
- Vita Ridola,
- Sabine Kroiss Benninger,
- Angela Mastronuzzi,
- Sarah Schott,
- Juliane Nees,
- Aram Prokop,
- Antje Redlich,
- Markus G. Seidel,
- Stefanie Zimmermann,
- Kristian W. Pajtler,
- Stefan M. Pfister,
- Pierre Hainaut,
- Christian P. Kratz
Affiliations
- Judith Penkert
- Pediatric Hematology and Oncology, Hannover Medical School
- Farina J. Strüwe
- Pediatric Hematology and Oncology, Hannover Medical School
- Christina M. Dutzmann
- Pediatric Hematology and Oncology, Hannover Medical School
- Beate B. Doergeloh
- Pediatric Hematology and Oncology, Hannover Medical School
- Emilie Montellier
- Univ. Grenoble Alpes, Inserm 1209, CNRS 5309, Institute for Advanced Biosciences
- Claire Freycon
- Univ. Grenoble Alpes, Inserm 1209, CNRS 5309, Institute for Advanced Biosciences
- Myriam Keymling
- Division of Radiology, German Cancer Research Center (DKFZ)
- Heinz-Peter Schlemmer
- Division of Radiology, German Cancer Research Center (DKFZ)
- Birte Sänger
- Pediatric Hematology and Oncology, Hannover Medical School
- Beatrice Hoffmann
- Pediatric Hematology and Oncology, Hannover Medical School
- Tanja Gerasimov
- Pediatric Hematology and Oncology, Hannover Medical School
- Claudia Blattmann
- Department of Pediatric Oncology, Hematology and Immunology, Olgahospital, Klinikum Stuttgart
- Sebastian Fetscher
- Department of Haematology and Oncology, Sana Hospitals
- Michael Frühwald
- Paediatric and Adolescent Medicine, University Medical Center Augsburg
- Simone Hettmer
- Division of Pediatric Hematology and Oncology, Department of Pediatric and Adolescent Medicine, University Medical Center Freiburg, University of Freiburg
- Uwe Kordes
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf
- Vita Ridola
- Department of Pediatric Oncology and Hematology, MITERA Children’s Hospital
- Sabine Kroiss Benninger
- Department of Oncology, University Children’s Hospital Zürich
- Angela Mastronuzzi
- Department of Haematology, Oncology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, IRCCS Bambino Gesù Children’s Hospital
- Sarah Schott
- Department of Obstetrics and Gynecology, University of Heidelberg
- Juliane Nees
- Department of Obstetrics and Gynecology, University of Heidelberg
- Aram Prokop
- Department of Pediatric Hematology/Oncology, Helios Clinic Schwerin
- Antje Redlich
- Pediatric Oncology Department, Otto von Guericke University Children’s Hospital
- Markus G. Seidel
- Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz
- Stefanie Zimmermann
- Pediatric Hematology and Oncology, University Hospital
- Kristian W. Pajtler
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Stefan M. Pfister
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Pierre Hainaut
- Univ. Grenoble Alpes, Inserm 1209, CNRS 5309, Institute for Advanced Biosciences
- Christian P. Kratz
- Pediatric Hematology and Oncology, Hannover Medical School
- DOI
- https://doi.org/10.1186/s13045-022-01332-1
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 5
Abstract
Abstract Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype–phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype–phenotype correlations encouraging further analyses.
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