Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

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

Research on Rare Diseases in Germany - Cancer Predisposition Syndrome Registry

Background: Cancer predisposition syndromes (CPS) are rare diseases that are associated with an increased risk of cancer due to genetic alterations. At least 8 % of all cases of childhood cancer are attributable to CPS. The CPS registry was launched in 2017 to learn more about CPS and to improve the care to those afflicted by these diseases. Methods: This is an internationally networked registry with associated accompanying studies that investigate cancer risks and spectra, the possibilities of cancer prevention, early detection and therapy. Results: For several of these syndromes, new insights into the cancer risks and cancer types as well as factors modifying cancer risk have been gained. In addition, experimental, psycho-oncological, preclinical and clinical studies were initiated. Conclusions: The CPS registry is an example of how progress can be made within a short period of time to the benefit of individuals with rare diseases through systematic data collection and research

Forschung zu Seltenen Erkrankungen in Deutschland - Das Krebsprädispositionssyndrom-Register

Hintergrund: Krebsprädispositionssyndrome (KPS) sind seltene Erkrankungen, die auf Grund von genetischen Veränderungen mit einem erhöhten Krebsrisiko einhergehen. Mindestens 8 % aller Krebserkrankungen im Kindesalter sind auf ein KPS zurückzuführen [1, 2]. 2017 wurde das KPS-Register eröffnet, um mehr über KPS zu lernen und um die Betreuung Betroffener zu verbessern. Methode: Es handelt sich um ein international vernetztes Register sowie daran angegliederte Begleitstudien, die die Krebsrisiken und -spektren, die Möglichkeiten der Krebsprävention und -früherkennung sowie der -therapie untersuchen. Ergebnisse: Für mehrere KPS wurden neue Erkenntnisse zu Krebsrisiken und Krebsarten sowie zu Faktoren, die das Krebsrisiko modifizieren, erworben. Zudem wurden experimentelle, psychoonkologische sowie präklinische und klinische Studien ins Leben gerufen. Schlussfolgerungen: Das KPS-Register ist ein Beispiel dafür, wie für Menschen mit Seltenen Erkrankungen innerhalb kurzer Zeit durch systematische Datensammlung und Forschung Fortschritte erzielt werden können

Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01332-1