Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.
Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.
Lanternier
Fanny
F
Université Paris V, Service de maladies infectieuses et tropicales, Centre de référence des mastocytoses, Hôpital Necker Enfants malades, Centre d'Infectiologie Necker-Pasteur, Paris, France.
Cohen-Akenine
Annick
A
Palmerini
Fabienne
F
Feger
Frédéric
F
Yang
Ying
Y
Zermati
Yael
Y
Barète
Stéphane
S
Sans
Beatrix
B
Baude
Cédric
C
Ghez
David
D
Suarez
Felipe
F
Delarue
Richard
R
Casassus
Philippe
P
Bodemer
Christine
C
Catteau
Adeline
A
Soppelsa
Frédérique
F
Hanssens
Katia
K
Arock
Michel
M
Sobol
Hagay
H
Fraitag
Sylvie
S
Canioni
Danièle
D
Moussy
Alain
A
Launay
Jean Marie
JM
Dubreuil
Patrice
P
Hermine
Olivier
O
Lortholary
Olivier
O
D000328:Adult; D017668:Age of Onset; D001706:Biopsy; D002648:Child; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008415:Mastocytosis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012867:Skin / Q000473:pathology
D019009:Proto-Oncogene Proteins c-kit