A new mutation affecting the ATP pocket of kit receptor in patients with GIST showing acquired resistance to Imatinib: A coupled experimental and modeling investigation

S. Pricl, A. Coslanich, M. Fermeglia, M. Ferrone, M. S. Paneni, E. Tamborini, S. Pilotti, M. A. Pierotti

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

A new mutation, T6701, affecting the ATP-binding pocket of the c-kit receptor was detected for the first time in patients with advanced gastrointestinal stromal tumors (GIST) undergoing Imatinib therapy. The analysis of the c-kit cDNA sequence of the nonresponding metastases revelaed a point mutation in exon 14, T2030C, resulting in the corresponding aminoacidic substitution T6701. The non-responding lesion showed a highly expressed and phosphorylated kit receptor, whereas the responding ones showed a weak it expression and activation. Superimposing the wild type structure on the mutated Imatinib complex structure showed that two moieties of Imatinib were incompatible with the fully-assembled, autoinhibited structure of the c-kit kinase.

Original languageEnglish
Title of host publicationAIChE Annual Meeting, Conference Proceedings
Pages2219-2221
Number of pages3
Publication statusPublished - 2004
Event2004 AIChE Annual Meeting - Austin, TX, United States
Duration: Nov 7 2004Nov 12 2004

Other

Other2004 AIChE Annual Meeting
CountryUnited States
CityAustin, TX
Period11/7/0411/12/04

ASJC Scopus subject areas

  • Engineering(all)

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    Pricl, S., Coslanich, A., Fermeglia, M., Ferrone, M., Paneni, M. S., Tamborini, E., Pilotti, S., & Pierotti, M. A. (2004). A new mutation affecting the ATP pocket of kit receptor in patients with GIST showing acquired resistance to Imatinib: A coupled experimental and modeling investigation. In AIChE Annual Meeting, Conference Proceedings (pp. 2219-2221)