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.
Bodemer
Christine
C
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
Hermine
Olivier
O
Palmérini
Fabienne
F
Yang
Ying
Y
Grandpeix-Guyodo
Catherine
C
Leventhal
Phillip S
PS
Hadj-Rabia
Smail
S
Nasca
Laurent
L
Georgin-Lavialle
Sophie
S
Cohen-Akenine
Annick
A
Launay
Jean-Marie
JM
Barete
Stéphane
S
Feger
Frédéric
F
Arock
Michel
M
Catteau
Benoît
B
Sans
Beatrix
B
Stalder
Jean François
JF
Skowron
Francois
F
Thomas
Luc
L
Lorette
Gérard
G
Plantin
Patrice
P
Bordigoni
Pierre
P
Lortholary
Olivier
O
de Prost
Yves
Y
Moussy
Alain
A
Sobol
Hagay
H
Dubreuil
Patrice
P
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