Fiche publication
Date publication
février 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOUVIER Anne-Marie
,
Dr CHAPUSOT Caroline
,
Dr GARRIDO Carmen
,
Pr LEPAGE Côme
Tous les auteurs :
Collura A, Lagrange A, Svrcek M, Marisa L, Buhard O, Guilloux A, Wanherdrick K, Dorard C, Taieb A, Saget A, Loh M, Soong R, Zeps N, Platell C, Mews A, Iacopetta B, De Thonel A, Seigneuric R, Marcion G, Chapusot C, Lepage C, Bouvier AM, Gaub MP, Milano G, Selves J, Senet P, Delarue P, Arzouk H, Lacoste C, Coquelle A, Bengrine-Lefevre L, Tournigand C, Lefevre JH, Parc Y, Biard DS, Flejou JF, Garrido C, Duval A
Lien Pubmed
Résumé
BACKGROUND & AIMS: Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses than patients with tumors without MSI, but have a poor response to 5-fluorouracil-based chemotherapy. A dominant-negative form of heat shock protein (HSP)110 (HSP110DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T(17) intron repeat, sensitizes the cells to 5-fluorouracil and oxaliplatin.We investigated whether HSP110 T(17) could be used to identify patients with colorectal cancer who would benefit from adjuvant chemotherapy with 5-fluorouracil and oxaliplatin. METHODS: We characterized the interaction between HSP110 and HSP110DE9 using surface plasmon resonance. By using polymerase chain reaction and fragment analysis, we examined how the size of somatic allelic deletions in HSP110 T(17) affected the HSP110 protein expressed by tumor cells. We screened 329 consecutive patients with stage II-III colorectal tumors with MSI who underwent surgical resection at tertiary medical centers for HSP110 T(17). RESULTS: HSP110 and HSP110DE9 interacted in a1:1 ratio. Tumor cells with large deletions in T(17) had increased ratios of HSP110DE9:HSP110, owing to the loss of expression of full-length HSP110. Deletions in HSP110 T(17) were mostly biallelic in primary tumor samples with MSI. Patients with stage II-III cancer who received chemotherapy and had large HSP110 T(17) deletions (>/=5 bp; 18 of 77 patients, 23.4%) had longer times of relapse-free survival than patients with small or no deletions (
Référence
Gastroenterology. 2014 Feb;146(2):401-11.e1.
