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Genomic Grade Index predicts postoperative clinical outcome of GIST

Authors
 F Bertucci  ;  P Finetti  ;  J Ostrowski  ;  WK Kim  ;  H Kim  ;  MA Pantaleo  ;  A Astolfi  ;  M Polkowski  ;  D Birnbaum 
Citation
 BRITISH JOURNAL OF CANCER, Vol.107(8) : 1433-1441, 2012 
Journal Title
 BRITISH JOURNAL OF CANCER 
ISSN
 0007-0920 
Issue Date
2012
MeSH
Antineoplastic Agents/therapeutic use ; Benzamides ; Female ; Gastrointestinal Stromal Tumors/drug therapy ; Gastrointestinal Stromal Tumors/genetics* ; Gastrointestinal Stromal Tumors/surgery ; Gene Expression Profiling ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Piperazines/therapeutic use ; Prognosis ; Pyrimidines/therapeutic use ; Treatment Outcome
Keywords
DNA microarray ; gene expression ; GIST ; imatinib ; profiling ; prognosis
Abstract
Background : Prognosis of localised gastrointestinal stromal tumour (GIST) is heterogeneous, notably for patients with AFIP intermediate or high risk of relapse, who are candidates to adjuvant imatinib. We hypothesised that gene expression profiles might improve the prognostication and help to refine the indications for imatinib. Methods : We collected gene expression and histoclinical data of 146 pre-treatment localised GIST samples treated with surgery alone. We searched for a gene expression signature (GES) predictive for relapse-free survival (RFS) and compared its performances to that of three published prognostic proliferation-based GES (Genomic Grade Index (GGI), 16-Kinase, and CINSARC) and AFIP classification. We also analysed a data set from 28 patients with advanced GIST treated with neo-adjuvant imatinib. Results : We identified a 275-gene GES (gene expression signature) predictive of RFS in a learning set and validated its robustness in an independent set. However, the GGI outperformed its prognostic performances, and those of the two other signatures and the AFIP intermediate-risk classification in two independent tests sets in uni- and multivariate analyses. Importantly, GGI could split the AFIP intermediate/high-risk samples into two groups with different RFS. Genomic Grade Index 'high-risk' tumours were more proliferative and genetically unstable than 'low-risk' tumours, and more sensitive to imatinib. Conclusion : GGI refines the prediction of RFS in localised GIST and might help tailor adjuvant imatinib.
Files in This Item:
T201206465.pdf Download
DOI
10.1038/bjc.2012.390
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Won Kyu(김원규)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158377
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