Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
2015 | journal article. A publication with affiliation to the University of Göttingen.
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Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
Kratz, C. P.; Franke, L.; Peters, H.; Kohlschmidt, N.; Kazmierczak, B.; Finckh, U. & Bier, A. et al. (2015)
British Journal of Cancer, 112(8) pp. 1392-1397. DOI: https://doi.org/10.1038/bjc.2015.75
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- Authors
- Kratz, Christian P.; Franke, L.; Peters, H.; Kohlschmidt, N.; Kazmierczak, B.; Finckh, U.; Bier, Andrea; Eichhorn, B.; Blank, C.; Kraus, Cornelia; Kohlhase, Juergen; Pauli, Silke; Wildhardt, G.; Kutsche, Kerstin; Auber, Bernd; Christmann, A.; Bachmann, N.; Mitter, D.; Cremer, F. W.; Mayer, K.; Daumer-Haas, C.; Nevinny-Stickel-Hinzpeter, C.; Oeffner, Frank; Schlueter, G.; Gencik, M.; Ueberlacker, B.; Lissewski, Christina; Schanze, I.; Greene, M. H.; Spix, C.; Zenker, Martin
- Abstract
- Background: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown. Methods: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry. Results: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR) = 10.5, 95% confidence interval = 5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia = 4; brain tumour = 3; acute lymphoblastic leukaemia = 2; rhabdomyosarcoma = 2; and neuroblastoma = 1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4. Conclusions: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.
- Issue Date
- 2015
- Status
- published
- Publisher
- Nature Publishing Group
- Journal
- British Journal of Cancer
- ISSN
- 1532-1827; 0007-0920