Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.
Adult mastocytosis is an incurable clonal disease associated with c-KIT mutations, mostly in exon 17 (D816V). In contrast, pediatric mastocytosis often spontaneously regresses and is considered a reactive disease. Previous studies on childhood mastocytosis assessed only a few patients and focused primarily on codon 816 mutations, with various results. In this study, we analyzed the entire c-KIT sequence from cutaneous biopsies of 50 children with mastocytosis (ages 0-16 years). A mutation of codon 816 (exon 17) was found in 42% of cases, and mutations outside exon 17 were observed in 44%. Unexpectedly, half of the mutations were located in the fifth Ig loop of c-KIT's extracellular domain, which is encoded by exons 8 and 9. All mutations identified in this study were somatic and caused a constitutive activation of c-KIT. There was no clear phenotype-genotype correlation, no clear relationship between the mutations and familial versus spontaneous disease, and no significant change in the relative expression of the c-KIT GNNK+ and GNNK isoforms. These findings strongly support the idea that, although pediatric mastocytosis can spontaneously regress, it is a clonal disease most commonly associated with activating mutations in c-KIT.
Service de Dermatologie, Hôpital Necker, CEREMAST, Centre de Référence des Mastocytoses, Faculté Necker, Université René Descartes Paris V, Paris, France. christine.bodemer@nck.aphp.fr
Christine
C
Bodemer
Olivier
O
Hermine
Fabienne
F
Palmérini
Ying
Y
Yang
Catherine
C
Grandpeix-Guyodo
Phillip S
PS
Leventhal
Smail
S
Hadj-Rabia
Laurent
L
Nasca
Sophie
S
Georgin-Lavialle
Annick
A
Cohen-Akenine
Jean-Marie
JM
Launay
Stéphane
S
Barete
Frédéric
F
Feger
Michel
M
Arock
Benoît
B
Catteau
Beatrix
B
Sans
Jean François
JF
Stalder
Francois
F
Skowron
Luc
L
Thomas
Gérard
G
Lorette
Patrice
P
Plantin
Pierre
P
Bordigoni
Olivier
O
Lortholary
Yves
Y
de Prost
Alain
A
Moussy
Hagay
H
Sobol
Patrice
P
Dubreuil
D000293:Adolescent; D017668:Age of Onset; D000818:Animals; D001706:Biopsy; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D002999:Clone Cells; D005091:Exons / Q000235:genetics; D005260:Female; D023281:Genomics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008407:Mast Cells / Q000473:pathology* / Q000502:physiology; D034701:Mastocytosis, Cutaneous / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
D019009:Proto-Oncogene Proteins c-kit