Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
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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; Eichhorn, B; Blank, C; Kraus, C; Kohlhase, J; Pauli, S; Wildhardt, G; Kutsche, K; Auber, B; Christmann, A; Bachmann, N; Mitter, D; Cremer, F W; Mayer, K; Daumer-Haas, C; Nevinny-Stickel-Hinzpeter, C; Oeffner, F; Schlüter, G; Gencik, M; Überlacker, B; Lissewski, C; Schanze, I; Greene, M H; Spix, C; Zenker, M.
In: BRIT J CANCER, Vol. 112, No. 8, 14.04.2015, p. 1392-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
AU - Kratz, C P
AU - Franke, L
AU - Peters, H
AU - Kohlschmidt, N
AU - Kazmierczak, B
AU - Finckh, U
AU - Bier, A
AU - Eichhorn, B
AU - Blank, C
AU - Kraus, C
AU - Kohlhase, J
AU - Pauli, S
AU - Wildhardt, G
AU - Kutsche, K
AU - Auber, B
AU - Christmann, A
AU - Bachmann, N
AU - Mitter, D
AU - Cremer, F W
AU - Mayer, K
AU - Daumer-Haas, C
AU - Nevinny-Stickel-Hinzpeter, C
AU - Oeffner, F
AU - Schlüter, G
AU - Gencik, M
AU - Überlacker, B
AU - Lissewski, C
AU - Schanze, I
AU - Greene, M H
AU - Spix, C
AU - Zenker, M
PY - 2015/4/14
Y1 - 2015/4/14
N2 - 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.
AB - 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.
U2 - 10.1038/bjc.2015.75
DO - 10.1038/bjc.2015.75
M3 - SCORING: Journal article
C2 - 25742478
VL - 112
SP - 1392
EP - 1397
JO - BRIT J CANCER
JF - BRIT J CANCER
SN - 0007-0920
IS - 8
ER -