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Cancer spectrum and frequency among children with Noonan, Costello, and
cardio-facio-cutaneous syndromes
#MMPMID25742478
Kratz CP
; 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 FW
; Mayer K
; Daumer-Haas C
; Nevinny-Stickel-Hinzpeter C
; Oeffner F
; Schlüter G
; Gencik M
; Überlacker B
; Lissewski C
; Schanze I
; Greene MH
; Spix C
; Zenker M
Br J Cancer
2015[Apr]; 112
(8
): 1392-7
PMID25742478
show ga
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.
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