Identification of Activating c-kit Mutations in Adult-, but not in Childhood-Onset Indolent Mastocytosis: A Possible Explanation for Divergent Clinical.

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Presentation transcript:

Identification of Activating c-kit Mutations in Adult-, but not in Childhood-Onset Indolent Mastocytosis: A Possible Explanation for Divergent Clinical Behavior Claudia Büttner, Beate M. Henz, Pia Welker Journal of Investigative Dermatology Volume 111, Issue 6, Pages 1227-1231 (December 1998) DOI: 10.1046/j.1523-1747.1998.00414.x Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Location of the primers P1–4 in the c-kit gene. The primers P1 to P4 are located in exon 11 of the c-kit gene, which contains the bp1700 at codon 560 critical for the T(r)G point mutation. Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Location of the primers P5–8 in the c-kit gene. The primers P5 to P8 are located in exon 17 of the c-kit gene, which contains the bp 2468 at codon 816 critical for the A(r)T point mutation. Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 PleI restriction analysis of DNA from adult-onset mastocytosis shows bands specific for the activating codon 816 c-kit mutation.PleI digested (+) and undigested (–) PCR products (length 114 bp) from DNA of adult-onset mastocytosis skin biopsies and of KU-812 and HMC-1 cells. Mutation-specific bands at 82 and 33 bp can be seen in the digested sample of HMC-1 cells and at 82 bp in both samples from adults (aM1 and aM6, corresponding to patients 12 and 17 inTable 1). Due to the small amount of mutated DNA in the clinical samples, the restriction bands at 33 bp could not be visualized. The digested DNA sample from KU-812 cells shows no mutation-specific restriction bands. The original data were digitally processed using a Hewlett-Packard Scan Jet IIcx. Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 PleI restriction analysis shows no mutation-specific bands in samples from childhood-onset mastocytosis.PleI digested (+) and undigested (–) PCR products (length 114 bp) from DNA of childhood-onset mastocytosis skin biopsies (cM1–4, corresponding to patients 1–4 inTable 1)and of KU-812 and HMC-1 cells. Mutation-specific bands at 82 and 33 bp appear only in the digested sample of HMC-1 cells. The original data were digitally processed using a Hewlett-Packard Scan Jet IIcx. Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 HphI restriction analysis from lesional skin of adult- and childhood-onset mastocytosis patients show bands specific for activating c-kit mutation in an adult specimen.HphI digested (+) and undigested (–) PCR products (length bp108) from DNA of adult- and childhood-onset mastocytosis skin biopsies, of KU-812 and HMC-1 cells. Mutation-specific bands at 51 and 58 bp can be seen in the digested DNA samples from HMC-1 cells and from an adult (aM5, corresponding to patient 16 inTable 1). Digested DNA samples from two children with urticaria pigmentosa (cM5 and cM8, corresponding to patients 5 and 8 inTable 1) and from KU-812 cells show no mutation-specific bands. The original data were digitally processed using a Hewlett-Packard Scan Jet IIcx. Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 No bp2468 A(r)T mutation in c-kit sequences from KU-812 cells. (a) Automated sequencing from HMC-1 cells shows heterozygous A(r)T mutation at position 2468 (arrow); (b) sequence from KU-812 cells shows wild-type sequence with adenine at position 2468 (arrow). Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 Automated sequencing of cloned c-kit DNA of one adult patient shows a heterozygous point mutation at position 2468 (arrows). (a) Wild-type sequence with adenine at position 2468 (arrow); (b) mutated sequence from the same patient with thymidine at position 2468 (arrow). Journal of Investigative Dermatology 1998 111, 1227-1231DOI: (10.1046/j.1523-1747.1998.00414.x) Copyright © 1998 The Society for Investigative Dermatology, Inc Terms and Conditions