Pediatric Mastocytosis Is a Clonal Disease Associated with D816V and Other Activating c-KIT Mutations

被引：279

作者：

Bodemer, Christine ^{[1
,2
,8
]}

Hermine, Olivier ^{[2
,3
,4
]}

Palmerini, Fabienne ^{[2
,5
,6
]}

Yang, Ying ^{[6
]}

Grandpeix-Guyodo, Catherine ^{[2
]}

Leventhal, Phillip S. ^{[7
]}

Hadj-Rabia, Smail ^{[8
]}

Nasca, Laurent ^{[5
,6
]}

Georgin-Lavialle, Sophie ^{[2
,3
]}

Cohen-Akenine, Annick ^{[7
]}

Launay, Jean-Marie ^{[9
]}

Barete, Stephane ^{[2
,3
]}

Feger, Frederic ^{[3
]}

Arock, Michel ^{[3
]}

Catteau, Benoit ^{[10
]}

Sans, Beatrix ^{[11
]}

Stalder, Jean Francois ^{[12
]}

Skowron, Francois ^{[13
]}

Thomas, Luc ^{[14
]}

Lorette, Gerard ^{[15
]}

Plantin, Patrice ^{[16
]}

Bordigoni, Pierre ^{[17
]}

Lortholary, Olivier ^{[2
,8
,18
]}

de Prost, Yves ^{[8
]}

Moussy, Alain ^{[7
]}

Sobol, Hagay ^{[5
,19
,20
]}

Dubreuil, Patrice ^{[5
,6
]}

机构：

[1] Univ Paris 05, Serv Dermatol, Hop Necker, F-75743 Paris 15, France

[2] Fac Med Necker Enfants Malad, CEREMAST, Ctr Reference Mastocytoses, Paris, France

[3] Univ Paris 05, Hop Necker, AP HP, CNRS UMR 8147, F-75743 Paris 15, France

[4] Hop Necker Enfants Malad, Serv Hematol Adulte, Paris, France

[5] Univ Mediterranee, Dept Oncol Genet Prevent & Depistage, Inst J Paoli I Calmettes, Marseille, France

[6] Ctr Rech Cancerol Marseille, INSERM U891, Lab Hematopoiese Mol & Fonct, Marseille, France

[7] AFIRMM, Paris, France

[8] Univ Paris 05, Paris, France

[9] Hop Lariboisiere, Serv Biochim & Biol Mol, F-75475 Paris, France

[10] CHU Lille, Hop Claude Huriez, Serv Dermatol, F-59037 Lille, France

[11] Hop Purpan, Serv Dermatol Venerol & Allergol, Toulouse, France

[12] CHU Nantes, Hop Hotel Dieu, Serv Dermatol, F-44035 Nantes 01, France

[13] Ctr Hosp Valence, Serv Dermatol, Valence, France

[14] Hop Hotel Dieu, Serv Dermatol, F-69288 Lyon, France

[15] CHU Trousseau, Serv Dermatol, F-37044 Tours, France

[16] Hop Laennec, Serv Dermatol, F-75340 Paris, France

[17] Hop Brabois, Dept Hematol Oncol, Vandoeuvre Les Nancy, France

[18] Hop Necker Enfants Malad, AP HP, Dept Malad Infect & Trop, Paris, France

[19] INSERM, CIC P 9502, F-13258 Marseille, France

[20] Univ Aix Marseille 2, F-13284 Marseille 07, France

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2010年 / 130卷 / 03期

关键词：

RECEPTOR TYROSINE KINASE; STEM-CELL FACTOR; MAST-CELL; CUTANEOUS MASTOCYTOSIS; SYSTEMIC MASTOCYTOSIS; TRANSMEMBRANE DOMAIN; GERMLINE MUTATION; STRUCTURAL BASIS; PHOSPHORYLATION; IDENTIFICATION;

D O I：

10.1038/jid.2009.281

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Adult mastocytosis is an incurable clonal disease associated with c-KIT mutations, mostly in exon 17 ((DV)-V-816). 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

引用

页码：804 / 815

页数：12

共 41 条

[1] A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib [J].