Uguquko lweGene lwe-Human EML4-ALK Fusion

Le khithi isetyenziselwa ukubona ngokwemigangatho iintlobo ezili-12 ze-mutation ze-EML4-ALK fusion gene kwiisampulu zezigulane zomhlaza wamaphaphu ezingezizo ezincinci zabantu kwi-vitro. Iziphumo zovavanyo zezereferensi yeklinikhi kuphela kwaye akufuneki zisetyenziswe njengesiseko sodwa sonyango oluzimeleyo lwezigulane. Iingcali zonyango kufuneka zenze izigqibo ezipheleleyo kwiziphumo zovavanyo ngokusekelwe kwizinto ezifana nemeko yesigulane, iimpawu zamayeza, impendulo yonyango, kunye nezinye izalathisi zovavanyo lwelebhu. Umhlaza wamaphaphu yeyona tumor ixhaphakileyo kwihlabathi liphela, kwaye i-80% ~ 85% yamatyala ngumhlaza wamaphaphu ongengomncinci weseli (NSCLC). Ukuhlanganiswa kwezakhi zofuzo ze-echinoderm microtubule-associated protein-like 4 (EML4) kunye ne-anaplastic lymphoma kinase (ALK) yinto entsha ekujoliswe kuyo kwi-NSCLC, i-EML4 kunye ne-ALK zifumaneka ngokwahlukeneyo ebantwini, ii-P21 kunye ne-P23 bands kwi-chromosome 2 kwaye zahlulwe malunga ne-12.7 yezigidi zeepayi zesiseko. Ubuncinane kukho iintlobo ezingama-20 ze-fusion ezifunyenweyo, phakathi kwazo ii-fusion mutants ezili-12 kwiTheyibhile 1 zixhaphakile, apho i-mutant 1 (E13; A20) yeyona ixhaphakileyo, ilandelwa zii-mutants 3a kunye ne-3b (E6; A20), ezimalunga ne-33% kunye ne-29% yezigulane ezine-EML4-ALK fusion gene NSCLC, ngokwahlukeneyo. Izithinteli ze-ALK ezimelwe yiCrizotinib ngamayeza ajoliswe kwi-molecule encinci ephuhliselwe ii-ALK gene fusion mutations. Ngokuthintela umsebenzi wengingqi ye-ALK tyrosine kinase, ukuthintela iindlela zayo ezingaqhelekanga zokubonisa, ngaloo ndlela kuthintela ukukhula kweeseli ze-tumor, ukuze kufezekiswe unyango olujoliswe kuzo lwee-tumor. Izifundo zeklinikhi zibonise ukuba iCrizotinib inezinga elisebenzayo elingaphezulu kwe-61% kwizigulane ezine-EML4-ALK fusion mutations, ngelixa ingenampembelelo phantse kwizigulane zohlobo lwasendle. Ke ngoko, ukufunyanwa kwe-EML4-ALK fusion mutation yeyona nto iphambili nesisiseko sokukhokela ukusetyenziswa kwamayeza eCrizotinib.