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CONCLUSION*
GÉNÉRALE*
!Ces!dernières!années,!la!recherche!dans!le!domaine!de!la!génétique!des!tumeurs!a!permis! d’aboutir!à!des!avancées!très!significatives.!Elle!a!en!particulier!été!très!éclairante!pour! identifier! les! mécanismes! qui! sousStendent! l’initiation! et! la! progression! des! cancers,! notamment! dans! le! côlon.! L’objectif! majeur! de! cette! recherche! est,! sur! un! plan! translationnel! et! clinique,! d’aboutir! à! l’identification! de! cibles! physiopathologiques! et! thérapeutiques! d’intérêt.! A! terme,! le! développement! de! cette! recherche! permettra! la! mise! en! œuvre! d’une! médecine! personnalisée! pour! chaque! patient,! tenant! compte! des! caractéristiques!de!sa!tumeur.!Mes!travaux!s’inscrivent!très!clairement!dans!ce!cadre!et! pourront!je!l’espère!aboutir!à!une!valorisation!plus!concrète!prochainement.!
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Sur! un! plan! physiopathologique! et! cognitif,! mes! travaux! se! sont! sinon! intéressés! à! certaines!conséquences!encore!très!peu!investiguées!de!l’instabilité!microsatellitaire!dans! le! génome! tumoral,! celles! relatives! aux! mutations! de! répétitions! non! codantes! que! ce! mode!majeur!d’instabilité!génétique!provoque!au!niveau!des!sites!donneurs/accepteurs! d’épissage!des!gènes.!La!mutation!d’HSP110!représente!à!ce!titre!un!exemple!de!ce!qui! pourrait! être! un! phénomène! redondant! dans! le! génome! de! ces! tumeurs,! à! savoir! la! survenue! de! mutations! provoquant! des! perturbations! d’épissage! en! nombre.! A! ce! titre,! elle!semble!contribuer!au!meilleur!pronostic!des!cancers!colorectaux!MSI!et!pourrait!être! responsable!de!certaines!de!leurs!caractéristiques!phénotypiques.!Très!récemment,!une! autre! étude! a! rapporté! que! le! gène! MRE11,! également! affecté! par! une! mutation! d’épissage! dans! ces! cancers,! était! associé! à! un! meilleur! pronostic! dans! les! cancers! colorectaux,! cette! foisSci! sans! rapport! avec! une! prise! en! charge! des! patients! par! chimiothérapie! 249.! Ces! résultats! suggèrent! que! l’instabilité! microsatellitaire! et! les! conséquences! qu’elle! peut! avoir! sur! la! transformation! de! la! cellule! sont! encore! des! domaines! à! explorer.! L’avènement! du! grand! séquençage! permettra! d’accélérer! nos! connaissances! dans! ce! domaine! et! le! laboratoire! d’accueil! s’est! déjà! très! largement! engagé!dans!cette!voie.!
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