Transcriptomics

Dataset Information

5

Imatinib targeting of KIT-mutant oncoprotein in melanoma


ABSTRACT: Metastatic melanoma is an aggressive treatment-refractory malignancy. Recently, c-Kit mutations were discovered in certain mucosal melanomas. A clinical trial was initiated with the c-Kit inhibitor imatinib mesylate. The first treated patient experienced dramatic clinical improvement within days, followed by major responses by PET/CT four weeks later at all sites of metastatic disease. Several established mucosal melanoma cell lines exhibited imatinib sensitivity in a fashion correlating with c-Kit mutational status. Although c-Kit mutations are uncommon in cutaneous melanoma, they may arise in geographically distinct subsets for whom use of c-Kit targeted kinase inhibition should be considered in a rational therapeutic approach. Keywords: Whole genome copy number analysis Copy number analysis using high-density SNP arrays to investigate genetic gains and losses involved in the genesis of mucosal and cutaneous melanoma. GSE8164_raw_copy_number_calls.xls contains raw copy number calls generated by dChip (build 5/2007) for GIST, K008, K029, M34, MEL1, MEL40, M6, and 5 Affymetrix controls (copy number identity 2 i.e. normal), which are available on the HapMAP site.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jyothi Jagannathan   Jun Zhou  Suzanne Mac Rae  Stephen F Hodi  Christopher Corless  George Demetri  Michael C Heinrich  David E Fisher  Stephen Hodi  Xiaofeng Jiang  Noah K Yuen  Philip Friedlander  Hans R Widlund  Annick van den Abbeele  Jonathan Fletcher  Andrea Kruse  Elsa Velazquez 

PROVIDER: E-GEOD-8164 | ArrayExpress | 2008-12-23

SECONDARY ACCESSION(S): GSE8164PRJNA101057

REPOSITORIES: GEO, ArrayExpress

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Publications

Imatinib targeting of KIT-mutant oncoprotein in melanoma.

Jiang Xiaofeng X   Zhou Jun J   Yuen Noah K NK   Corless Christopher L CL   Heinrich Michael C MC   Fletcher Jonathan A JA   Demetri George D GD   Widlund Hans R HR   Fisher David E DE   Hodi F Stephen FS  

Clinical cancer research : an official journal of the American Association for Cancer Research 20081201 23


PURPOSE: Melanoma subtypes based on anatomic location and UV light exposure can be further classified based on genetic alterations recently identified. Mutations and gene amplification in KIT have been described in a significant percentage of mucosal and acral melanomas. We recently reported a patient with metastatic mucosal melanoma harboring a known KIT mutation treated with imatinib mesylate who experienced a major response. Biological effects of KIT inhibition in these melanomas remain poorl  ...[more]

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