A novel K509I mutation of KIT identified in familial mastocytosis—in vitro and in vivo responsiveness to imatinib therapy

Zhang, Ling Yan; Smith, Matthew L.; Schultheis, Beate; Fitzgibbon, Jude; Lister, T. Andrew; Melo, Junia V.; Cross, Nicholas C.P.; Cavenagh, Jamie D.

doi:10.1016/j.leukres.2005.08.015

« Previous Next »Leukemia Research
Volume 30, Issue 4 , Pages 373-378, April 2006

A novel K509I mutation of KIT identified in familial mastocytosis—in vitro and in vivo responsiveness to imatinib therapy

Ling Yan Zhang
- Wessex Regional Genetics Laboratory, Salisbury, UK
Matthew L. Smith
- Cancer Research UK Medical Oncology Unit, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Beate Schultheis
- Department of Haematology, Imperial College and Hammersmith Hospital, London, UK
Jude Fitzgibbon
- Cancer Research UK Medical Oncology Unit, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
T. Andrew Lister
- Cancer Research UK Medical Oncology Unit, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
Junia V. Melo
- Department of Haematology, Imperial College and Hammersmith Hospital, London, UK
Nicholas C.P. Cross
- Wessex Regional Genetics Laboratory, Salisbury, UK
Jamie D. Cavenagh
- Department of Haematology, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
- Corresponding author. Tel.: +44 207 601 8202; fax: +44 207 601 8201.

Received 12 April 2005 published online 07 March 2011.

Abstract

KIT mutation has been implicated in sporadic mastocytosis, yet clusters in only a few sites in the molecule. For those malignancies associated with KIT mutation or over-expression, imatinib offers a specific therapeutic option, yet it has no effect on D816V mutation commonly seen in sporadic mastocytosis. The majority of cases of familial mastocytosis seem to lack KIT mutation. We report a kindred with mastocytosis in whom in vitro and in vivo sensitivity to imatinib was demonstrated. Mutation analysis of the KIT coding region in this family identified a novel A>T mutation at nucleotide 1547 [K509I] in exon 9 in both of the affected patients.