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Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during imatinib mesylate treatment

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Abstract

Purpose

Imatinib mesylate showed a sustained objective response in patients with advanced gastrointestinal stromal tumors (GISTs) since its introduction in 2001. Here we reported genetic changes during imatinib mesylate treatment especially when the patient had partial response or stationary disease.

Materials and methods

Between 2001 and June 2005, 44 advanced GIST patients were treated with imatinib mesylate. Among them, five patients (11.9%) (four with partial response and one with stationary disease) received surgical treatment during imatinib mesylate treatment. We compared the genetic status of each tumor in the five patients before and after imatinib mesylate treatment.

Results

Symptomatic gallbladder stone with or without cholecystitis (two patients), lower GI bleeding (one patient), upper GI bleeding (one patient), and enterocutaneous fistula (one patient) comprised the indications for operation. Before imatinib mesylate treatment, four of the five patients displayed deletion mutation and one patient displayed point mutation in exon 11. After treatment, one patient developed second novel missense mutation in exon 17 with acquired resistance since he was administered with only half dose of imatinib mesylate. The other four patients taking the same dose of imatinib mesylate exhibited identical mutation to the previous lesions.

Conclusions

Necrosis of large and bulky tumors after imatinib mesylate therapy might be the reason of gastrointestinal hemorrhage and enterocutaneous fistula requiring surgical intervention. Imatinib mesylate could induce acquired resistance during treatment and second novel mutation might be the reason.

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Acknowledgement

The authors gratefully acknowledge Novartis (Taiwan) for the financial support of the PET and genetic analysis.

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Authors and Affiliations

  1. Department of Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan

    Chun-Nan Yeh, Tsung-Wen Chen, Yi-Yin Jan & Miin-Fu Chen

  2. Department of Nuclear Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

    Feng-Yuan Liu

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  1. Chun-Nan Yeh
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  2. Tsung-Wen Chen
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  3. Feng-Yuan Liu
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  4. Yi-Yin Jan
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  5. Miin-Fu Chen
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Correspondence to Chun-Nan Yeh.

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Yeh, CN., Chen, TW., Liu, FY. et al. Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during imatinib mesylate treatment. Langenbecks Arch Surg 391, 615–621 (2006). https://doi.org/10.1007/s00423-006-0103-z

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  • DOI: https://doi.org/10.1007/s00423-006-0103-z

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