Đang tải... (xem toàn văn)
DOI 1 () 31276/VJST 64( 12) 05 09 Khoa hoc Y Difpc I Y hoc cd sd Khao sat dot bien mot so gen lien quan den ung thir phoi khong te bao nho bang ky thuat giai trinh tu the he moi Tran Thj Huyen Trang1,[.]
DOI: 1().31276/VJST.64( 12).05-09 Khoa hoc Y - Difpc I Y hoc cd sd Khao sat dot bien mot so gen lien quan den ung thir phoi khong te bao nho bang ky thuat giai trinh tu the he moi Tran Thj Huyen Trang1, Trjnh Le Huy1,2, Dao Ngoc Bac1, Luong Thj Lan Anh1,2, Doan Thj Kim Phupng12, Nguyen Thi Trang1, Dao Thj Trang1, Nguyen Thi Duyen1, Vu Thj Ha1,2* T r u o n g D a i hoc Y H a N o i 2B en h vien D a i hoc Y H a N o i N g a y n h a n b a i /5 /2 2 ; n g a y c h u y e n p h a n b ie n /5 /2 2 ; n g a y n h a n p h a n b ie n /6 /2 2 ; n g a y ch ap n h a n d a n g /6 /2 2 Tom tat: Cho den nay, ung thir phoi (UTP) la mot nhung benh ung thu dune hieu ro ve co che phan tir, co ty le mac va tu* vong cao dan so chung Phat hien cac dot bien gen lien quan den UTP dong vai tro quan de chi djnh phuong phap dieu trj dich (Tyrosine kinase inhibitors - TKI), tir cai thien thin gian song khong tien trien benh cua benh nhan Nghien cuu dune thuc hien nham khao sat mot so dang dot bien gen lien quan den UTP khong te bao nho (KTBN) bang ky thuat giai trinh tu* the he moi (Next-generation sequencing - NGS) tren mau mo sinh thiet cua benh nhan Nghien ciru dune thyc hien bitng phinrng phap mo ta cat ngang tren 40 benh nhan UTPKTBN dirpe xet nghiem phat hien dot bien gen tren mau mo bang NGS Ket qua cho thay, da so benh nhan la nam gioi (70,0%), tren 60 tudi (65%), if giai doan muon (100%) va chua dieu trj gi (85%) 26/40 benh nhan co phat hien dot bien, dot bien co tan suat cao nhat tren gen EGFR (27,5%) va KRAS (20,0%), tiep theo la ALK (12,5%), BRAF (5,0%), khong phat hien cac dot bien tren NRAS, ROS1 va PIK3CA Tan suat cac dang dot bien lien quan den tinh nhay cam thuoc dich kha cao, khong phat hien cac dang dot bien khang thuoc Tir khoa: dieu trj dich, dot bien gen, giai trinh tir the he moi, ung thir phoi khong te bao nhd Chi so nhan loai: 3.1 Bit van de N G S la m o t tron g n h u n g k y th u at h ie n d a i, c h o p h e p d o c trinh tu v b i d o d c o th e b a n g c a h e g e n (h a n g ty b a se ) K h a c v b i c a c U T P la b en h u n g th u p h o b ie n th u h v a la n g u y e n n h an g a y tu v o n g h a n g d au tren th e g ia i v a o n a m 2 , tro n g d o U T P K T B N la lo a i p h o b ie n n h a t (c h ie m -8 % to n g s o c a U T P ) [1 ] T V ie t p h u o n g p h ap g ia i trinh tu S a n g e r tru y en th o n g c h i c h o p h ep d o c trin h tu v b i d o d a i n h o tren c a c g e n d ic h v a q u y trin h p h u c tap k h i m u o n p h a t h ie n n h ie u g e n d ic h , N G S c u n g ca p k h a n a n g c a o h o n g ia i d o a n m u o n k h i c a c d e p h a t h ie n c a c g e n m b i, d in h lu p n g c a c b ie n th e h ie m g a p v a c o p h u o n g p h a p d ie u tri tru y en th o n g it h ie u q u a, v i v a y s u p h a t trien th e x a c d in h c a c th a y d o i d o n n u c le o tid tren h a n g n g h in v u n g m u c c u a lie u p h a p T K I m o m o t h u d n g d ie u tri m b i c h o b e n h n h an tie u , th a m c h i c a h e g e n N a m p h an Ion b e n h n h a n p h at h ie n U T P u n g th u n o i c h u n g v a U T P n o i rien g H a u h e t c a c th u o c d ic h k h o n g V ie t N a m , T K I d u a v a o d o t b ie n g e n d a b u b c d a u d u p e ap g a y c h e t te b a o u n g th u m o t e a c h ca p tin h m a la m c h o c h u n g b i u c c h e p h at trien t u p h a t h o a c c h u y e n d a n g sa n g tin h tran g y e n la n g T u y n h ie n , h ie u q u a c u a th u o c T K I p h u th u o c v a o tin h tran g d o t b ie n c a c g e n m a h o a c a c p r o te in n a m tro n g c o n d u o n g tin h ie u te b a o u n g th u H ie n n a y , n h ie u th u th e la d ic h d ie u tri U T P d a d u p e u n g d u n g tro n g d ie u tri la m sa n g n h u EGFR, ALK, B RAF d u n g p h o b ie n h o n b b en h n h a n m a c U T P g ia i d o a n m u o n D a c o m o t s o n g h ie n c u u tru b c d a y v e d o t b ie n g e n tro n g U T P n h u n g tap tru n g ch u y e u v e g e n to a n b o g e n EGFR EGFR b m o t s o e x o n m a c h u a k h a o sat d u p e c u n g n h u c a c g e n k h a c c o lie n q u an tb i UTP H o n n u a , s u p h at trien c u a k y th u at N G S d a g o p p h an phat h ien c h o th a y n g a y c a n g n h ie u c a c b ie n th e m b i d u p e u n g d u n g tro n g T K I V i h ie u q u a la m sa n g to t h o n , th o i g ia n s o n g k h o n g tie n trien v a th b i v a y , c h u n g to i tie n h an h n g h ie n c u u n a y n h a m m u c tie u k h a o sat g ia n s o n g to n g th e k e o d a i h o n s o v o i d i 6u tri h o a c h i t d o n th u in m o t s o d a n g d o t b ie n g e n lie n q u a n d e n U T P K T B N b a n g N G S tren [2 ] T u y n h ie n , sa u m o t th b i g ia n d ie u tri, p h an lb n b e n h n h an x u a t m a u m o sin h th ie t c u a b e n h nh an h ien tin h tran g k h a n g th u o c , d a y c u n g la th a ch th u c lb n tr o n g v ie c Do i tityng va plulling phap nghien ciili lin g d u n g d ie u tri c u a lie u p h ap n ay M o t s o d o t b ie n g e n k h a c n h u KR.4S, R O S1, P IK 3C A , N R A S D o i titffn g c u n g la n h u n g d o t b ie n th u b n g g a p b e n h n h an U T P K T B N tai B e n h v ie n D a i h o c Y H a N o i , hr tro n g U T P K T B N v a d a n g d u p e n g h ie n c iiu p h at trien c a c th u o c TKJ d u a tren n h u n g d ic h p h a n tu n ay V i v a y , v ie c x a c d in h d an g th a n g /2 d e n th a n g /2 2 Tieu chudn chon m au: d o t b ie n g e n tren b e n h n h a n U T P K T B N rat q u an tro n g d e lu a c h o n chin d o a n l i e dpnh U T P K T B N VII (4(L co d ay d o d u n g tin ve hanh benh U T P k i t q n a g m p l a n b e n h phuerng p h a p d ie u trj p h u h o p , th e o d o i s u tai p h at c u a k h o i u v a (th e o tie u ch u a n cu a A J C C c a i th ie n ty le s o n g c u a b en h n h an c h in h , tie n s u g ia i d o a n 'Tacgia lien he: Email: vuthiha@hmu.edu.vn 64(12) 12.2022 Dupe Khoa hoc Y - Difclc I Y hoc cd sd k i t q u a g ia i p h lu b en h M a u m o d u g c s u d u n g la m o s in h th ie t d u e D etection o f gene m utation related to non-sm all cell lung cancer using next-generation sequencing Thi Huyen Trang Tran1, Le Huy Trinh1’2, Ngoc Bac Dao1, Thi Lan Anh Luong1,2, Thi Kim Phuong Doan1,2, Thi Trang Nguyen1, Thi Trang Dao1, Thi Duyen Nguyen1, Thi Ha Vu1,2* tron g k h o i n e n (F F P E ) Tach c h iit D N A : T a c h c h ie t D N A tir m a u m o U T P s u d u n g b o h o a c h a t Q IA a m p D N A F F P E T is s u e (Q ia g e n , M y ) v a g D N A ( D N A g e n o m e ) h o a ta n tro n g p i e lu tio n buffer C hudn bi th u vien: D N A sa u k h i ta ch c h ie t d u g c ch u a n b i th u v ie n b a n g b o k it N E B n e x t d s D N A fra g m en ta se v a N E B n e x t M u ltip le x O lig o s D u a l S a n p h a m sa u k h i d u g c c h g n lg c s e d u g c k h u ech d a i q u a P C R b an g c a p m o i P in d e x (c h u a trin h t u m a h o a m a u ) v a P adapter S a n p h a m D N A sa u k h i k h u e c h d a i s e d u g c ‘H a n o i M ed ica l U niversity 2H a n o i M edical U niversity H o sp ita l R e c e iv e d M a y 2 ; a c c e p te d tin h sa c h b a n g K A P A Pure B e a d s (K A P A b io s y s te m s ) L am gia u cac p h a n m anh D N A tic g en m uc tieu: Ju n e 2 San pham P C R tir b u d e ta o th u v ie n s e d u g c tie n h a n h la i v d i h o n h o p m a u d o c o c h u a g e n v a g a n b io tin d a c h ie u c h o c a c g e n m u c tie u Q u y Abstract: trinh sir d u n g th e o b o k it x G e n L o c k d o w n R e a g e n ts C a c m a u To date, lung cancer is one of the most well-understood cancers in terms of molecular mechanisms, with high incidence and mortality rates in the population Detecting lung cancerrelated gene mutations plays a vital role in offering targeted therapy, thereby improving the progression-free survival and overall survival rates of patients This study aims to identify some clinical features and factors related to non-small cell lung cancer and detect some types of gene mutations related to non small cell lung cancer by new-generation sequencing techniques on biopsy tissue samples of patients 40 patients with non-small cell lung cancer who were tested to detect gene mutations in biopsy tissue samples by next-generation sequencing Results showed the majority of patients were male (70%), over 60 years old (65%), in the late stage (100%), and have not received any treatment (85%) 26/40 patients have detected mutations, in which mutations are most frequently in EGFR (27.5%) and KRAS (20.0%), followed by ALK (12.5%), BRAF (5.0%), did not detect mutations on NRAS, ROS1, and PIK3CA The rate of mutations related to the target drug susceptibility was quite high, no resistant mutants were detected Keywords: gene mutation, next-generation non-small cell lung cancer, target therapy sequencing, d u g c th ie t k e v a t o n g h g p b d i x G e n p a n e l (ID T ) Toi m q u y trinh g id i trinh tu N G S v&i sau l&n: P h an ca t v a c h g n lg c k ic h th u d e g D N A tir c h u n g duom g (c h u n g to i s u d u n g T r u -Q l v a E M L -A L K R e fe r e n c e S tan d ard tir H a n g H o r iz o n la m c h u n g d u o n g ) g D N A tu c a c c h u n g d u om g m a n g d o t b ie n v a tu m a u k h o n g m a n g d o t b i l n s e d u g c p h a n c a t b a n g b o k it N E B n e x t d s D N A fra g m en ta se G idi trinh tu N G S : M a u s in h th ie t m o sa u k h i d u g c ta c h c h ie t, ch u a n b i th u v ie n v a la m g ia u g e n m u c tie u s e d u g c tie n h a n h g ia i trinh tu tren h e th o n g m a y g ia i trin h tu g e n th e h e m od M iS e q (Illu m in a ) P han tich k et qua g id i trinh tu: C a c b ie n th e d i tru y en d u g c k h a o sa t b a o g o m : d o t b ie n d ie m , m a t d o a n v a c h e n d o a n n g a n (duori 20 n u c le o tid e ) tro n g v iin g m a h o a (c o d in g r e g io n ) v a v im g la n c a n v o i in tron ( - /+ n u c le o t id e tir e x o n ) c u a c a c g e n K R A S, A L K , R O S1, B R A F va N R A S EGFR, C ac gen khac k h on g d u g c k h a o sa t tro n g n g h ie n c u u n ay C a c d o t b ie n lie n q u an d e n y n g h ia la m sa n g c u a c a c g e n E G F R , K R A S, N R A S, A L K , B R A F va RO S1 d u g c k ie m tra D o t b ie n c o y n g h ia la m s a n g d u a tren c a c lo a i th u o c d u g c c h a p th u a n b d i C o q u a n Q u a n ly th u o c v a T h u c p h a m H o a K y (F D A ) v a h u d n g d an c u a M a n g lu d i U n g th u q u o c g ia H o a Classification number: 3.1 K y (N C C N ) P han tich thong ke: Tieu chudn loai tru: C a c tru d n g h o p k h o n g d ap u n g it n h at m o t tro n g c a c tie u ch u a n lira c h o n tren K6t qua Phucmg phap nghien cuu Thiet ke nghien c m : C o m au nghien c m : Q u a n ly , p h a n tic h th o n g tin v a x u ly sd lie u b a n g p h a n m e m th o n g k e S P S S Dae diem lam sang vd mot so yeu to lien quan UTPKTBN N g h ie n c u u c a t n g a n g , m o ta b en h nh an B e n h n h an d a p u n g tie u cfauan lira c h o n s e d irg e d a n h g ia v a g h i n h an c a c th o n g tin la m sa n g Q u a trinh d a n h g ia tin h tran g d o t b ie n m o t s o g e n lie n q u an K d t q u a b a n g c h o th ay, d o tu o i k h d i p h at tru n g b in h la tu o i, tro n g d o c h u y e u la n h o m tu o i tren (6 % ) N a m g id i m a c b e n h c h ic m ty le % , n h ie u horn n u g id i (3 % ) C o 12 tru d n g h g p U T P K T B N c o tidn s u g ia d in h 1-2 n g u d i m a c u n g th u (c h ie m % ), tat c a c a c b e n h n h an d e u th u o c g ia i d o a n III-IV , tro n g d o 15 L T P K T B N b a n g k y th u at N G S tru d n g h o p c h u a c o d i c a n x a (c h ie m ,5 % ) v a Thu thap va xir ly m du m o sinh thiet: tru d n g h g p d i T h u th ap m a u m o sin h ca n n h id u c o q u a n ( c h i lm 15% ) T an su a t b en h n h an c h u a d ie u tri d u e t sa u k h i b e n h n h an d a d u g c c h a n d o a n x a c d jn h U T P d u a v a o c h ie m c a o nhdt v d i tru d n g h g p (8 % ), tn r d n g h o p d a d ie u tri 64( 12) 12.2022 Khoa hoc Y - DUpc I Y hoc cO sd h o a x a tri (1 % ), trtrong h o p d a p h a u th u at (2 ,5 % ) v a tru o n g Bang Phan b6 dot bien gen EGFR h o p d a n g d ie u tri T K I (2 ,5 % ) H a u h e t c a c b e n h n h an d e u th u oc V j t r i exon D ang d t bien N ucleotid th ay drii m o v a y (2 ,5 % ) Exon 18 G719A c.2156G>C Bang £>ac diem djch te, lam sang, can lam sang cua doi tirong nghien cltu Exon 19 Mat doan Exon 21 L858R U T P b ie u m o tu y e n c h ie m ,5 % c h i c o tn rb n g h o p U T P b ieu T a n so (n) T an su a t (% ) 9,1 36,4 54,5 11 100 c.2573T>G T6ng D a c d ie m T n s6 (n ) T in s u i t (% ) K R A S, T ren g e n Tuoi khcri phat ± ,9 < 60 14 35% lai G A , G V v a G C d eu c h ie m t i n su a t 12,5% (b a n g ) Tren >60 26 65% gen Nam 28 70,0% tnrcm g h o p Nu 12 30,0% Bang Phan bo mot so dang dot bien gen KRAS K hong co 28 70,0 1-2 ngudri mac 12 30,0 n h at la d a n g d o t b ie n sai n g h ia G C (c h ie m % ), c a c d a n g c o n Gicri tinh ALK c h i p h at h ie n d a n g d o t b ie n d u n g h o p g e n V j tr i exon Tien su gia dinh c h i p h a t h ie n d o t b ie n tren e x o n , g a p n h ieu Tuoi trung binh > ngudi m ac 0 Giai doan I-II 0 40 D ang d o t b iln N ucleotid th ay d5i T in s i (n) T an su a t (% ) G12A c.35G>C 12,5 G12C C.34G>T 50.0 G12V c.35G>T 12.5 G13C c.37G>T 123 100 Exon G iai doan benh Giai doan III-IV 100 D i can c o quan 19 47,5 D i can nhieu c o quan 15,0 K hong di can xa 15 37,5 T6ng Tinh trang di can A L K -E M L v b i Chua dieu tri 34 85,0 Phau thuat 2,5 H oa xa tri 10,0 TKI 2,5 U TP b ieu m o tuyen 39 97,5 U TP te bao vay 2,5 T ren g e n B RA E , hop dot bien sai nghia tren lan lirpt la Y600E va G596V p h at h ie n tnrcm g c o d o n k h a c n h au c o d a n g d o t b ie n (b a n g ) T inh trang dieu tri G iai phau benh Mot so dang dot bien gen lien quan den UTPKTB.X Bang Phan bo mot so dang dot b*6n gen BRAF V jtriexon Dangdftbiia V 600E c|T99T>A E xon15 G 596V cnPG>T T ong * t*.d m in im i i » m T an su a t p h a t h ie n d o t b ie n la % , tro n g d o d o t b ie n g e n E G F R (2 ,5 % ), c a c g e n K R A S, A L K v a B R A F lan lu p t la , 12 ,5 v a 5% , k h o n g g a p c a c d o t b ie n tren g e n R O S E X R A S v a P IK 3C A (b a n g 2) c h ie m tan su a t c a o nh at la Bang Phan bo cac loai dot bien T r o n g benh nhan tham gia nghien cuu, ty le nanvnir la 2,3/1, d o t u o i tr u n g binh mac benh la 62 (dao dong tu 41 d£n t u o i ) , h a y g a p n h a t la nhom tu o i tren 60 (65%) Tiong y van c u n g n h u c a c n g h ie n curu g a n d a y tren the g i a i deu cho thay r a n g , U T P g a p n h ie u h o n n a m gicri, ket q u a n a y c u n g p h u h o p t» p * T a n so (n ) T a n su a t (% ) EGFR 11 27,5 KR.4S ,0 ALK 12,5 m u o n ( g i a i d o a n I I I - I V ) , tr o n g d o c o 15% t r u a n g h o p c o v o i n h ie u n g h ie n c u u v e U T P tn r d c d a y ta i V ie t N a m V e d a c d ie m la m s a n g , ta t c a c a c b e n h n h a n d e u giai doan di can BRAF 5,0 x a it n h a t c o q u a n v a d a s o c a c c a d e u c h u a d ie u trj ( % ) 12 ROSI 0 tn r d n g h o p c o t i e n s u g i a d in h -2 n g u o i m a c u n g th u (3 % ) XRAS 0 PIK3CA 0 K h dog c o d o t b ien 14 35,0 T ong 40 100 K e t q u a n a y c u n g p h u h o p v o i n g h ie n ctru c u a c a c tac gia V ie t N a m T h e o n g h ie n c u u c u a H A T D a n g v a c s ( 2 ) [ ] t u o i tr u n g b in h la , ,6 % tru cm g h o p th u o c g ia i d o a n III-IV ,4 % b e n h n h a n c h u a d ie u tri g i C a c b e n h n h a n tr o n g K et q u a b a n g c h o th ay, tro n g 11 b e n h n h a n p h a t h ie n d o t b»en tren EGFR, ashla tren e x o n ■afaia tren e x o n 19(36.4%) d a n g d o t b ie n c h ie m ty le c a o n h at la d o t b ie n sa i 21 (5 ,5 % ), it g a p n h at la tru b n g h o p d o t b ie n sai 18 (9 ,1 % ) v a c o tnrcm g h o p m a t d o a n tren e x o n GSeNGHiViet Nam 64( 12) 12.2022 cu u cu a ch u n g to i d eu nghien g ia i d o a n m u o n d ie u n a y c o the giai lira chon dieu tri truyen t h o n g ( p h a u th u a t, h o a x a tr i) t h u o n g it h ie u q u a doi voi benh n h a n o g ia i d o a n m u o n D o n g t h o i d V ie t N a m phan ion beak n h a n U T P d u p e p h a t h ie n a g ia i d o a n m u o n da co cac b i n t h ic h d o c h i d in h x e t n g h ie m d o t b ie n g e n U T P n h a m t h u o c T K I tr e n la m s a n g k h i c a c p h u o n g p h a p Khoa hoc Y - Di/pc I Y hoc cd sd h ie n la m s a n g rd r a n g , It c a c tr u d n g h o p p h a t h ie n b e n h s d m n h a u v d i c a c p h u o n g p h a p h o a tri k h a c n h a u M o t s d n g h ie n d o y t h u c q u a n t a m , c h a m s o c s u e k h o e d in h k y c u a n g u d i c u u tr e n t h e g i d i p h a t h i e n t y le d o t b ie n d a n c h u a c a o U T P d i t r u y e n rat h i e m g a p v i v a y t i e n s u g i a n h d tn b e n h n h a n U T P K T B N k h o n g d a p u n g v d i d ie u tri T K I KRAS k h a c a o tr o n g KRAS d in h m a c u n g t h u c h u y e u d o c a c b a t t h u d n g n id i p h a t s in h [7 ] , T u y n h ie n , v i e c s u d u n g tin h tr a n g d o t b ie n v a k h o n g c o k h a n a n g d i t r u y e n s a n g t h e h e s a u T u y n h ie n , m o t d a u h i e u t i e n l u p n g x a u tr o n g d i e u tri T K I v a n c o n g a y d i e u n a y la i c h o t h a y g a n h n a n g b e n h ta t u n g t h u n g a y c a n g tr a n h c a i, d o k e t q u a k h o n g t h o n g n h a t t u c a c n g h ie n c u u p h a n ta n g d o i v d i m o i g i a d in h v a c a x a h o i T r o n g s o b e n h n h a n tic h to n g h o p k h a c n h a u C a c d o t b ie n U T P K T B N d u p e n g h i e n c u u , u n g t h u b i e u m o t u y e n c h ie m d o t b i e n p h o b id n n h d t G C , k h i c u n g td n ta i v d i b i e u h ie n ta n s u a t c h u y e u ( ,2 % ) , c h i p h a t h ie n t r u d n g h o p u n g P D L tr o n g k h d i u c u a b e n h n h a n d u p e c h o la c d t i e n l u p n g t h u b i e u m o v a y ( ,8 % ) K e t q u a c u a c h u n g t o i p h u h o p v o i x a u , v i v a y x e t n g h ie m d o t b ie n n g h i e n c u u ta i c a c q u o c g i a k h a c n h a u , c a c k e t q u a p h a n t i c h b e n h n h a n c h o li e u p h a p m i e n d j e h l a l p i ic h t i e m n a n g tr o n g d e u c h o t h a y U T P b i e u m o t u y e n v a b i e u m o v a y la d a n g t o n t u o n g la i [7 ] t h u o n g h a y g a p n h a t K RAS, KRAS c h u n g t o i p h a t h i e n tr u d n g h o p c o d o t b i e n g e n li e n q u a n c u u n a y la d u n g h o p g e n la d a n g d o t b ie n ALK A L K -E M L d a c b i e t la d a n g tr o n g v i e c l u a c h o n D a n g d o t b ie n d u y n h a t g a p tr e n g e n T r o n g s o b e n h n h a n th a m g i a n g h i e n c u u , b a n g N G S , nhu ALK tr o n g n g h ie n c h i e m ,5 % , d a y c u n g th u d n g g a p n h a t th e o c a c b a o c a o tra d e U T P , c h i e m % T r o n g d o , d o t b i e n tr e n g e n E G F R ( ,5 % ) A L K ( % ) v a d a y T v le n a y c a o hem s o v d i c a c n g h i e n c u u d a c o n g b o S u K R A S ( % ) la p h o b i e n n h a t, d o t B R A F (5 % ) h i e m g a p h o n v a k h o n g g e n R O S , N R A S v a P IK C A K e t q u a k h a c b ie t n a y c o t h e d o s d l u p n g b e n h n h a n t h a m g i a n g h ie n g a p c a c d o t b i e n tr e n c u u c u a c h u n g to i c o n h a n c h e n e n ty le p h a n b o d o t b ie n c o n a y c u n g tu o n g tu v d i s u c h e n h le c h g i u a c a c n g h i e n c u u va b ie n n g h ie n c u u c u a c u a H A T D a n g v a c s ( 2 ) [ ] tr e n b e n h n h a n U T P K T B N p h a t h ie n 6 % t r u d n g h o p m a n g it n h a t m o t b ie n d o i g e n c d li e n q u a n v e m a t la m s a n g , ( ,3 % ) v a KRAS n h a t, tid p t h e o la va NRAS EGFR ( % ) la c a c g e n b i d o t b ie n t h u d n g g a p ALK ( ,4 % ) , RO S1 ( ,9 % ) , BRAF ( ,1 % ) D o t b i e n tr e n g e n h ie m g a p h o n v d i tr u d n g h o p K e t q u a n a y c u n g t u o n g t u n h u c a c n g h i e n c u u k h a c , d o t b ie n tr e n g e n BRAF la m o t t r o n g n h u n g d o t b i e n g e n h i e m g a p d UTPKTBN ( ,6 % ) X u h u d n g n a y c u n g d u p e b a o c a o t a i m o t C a c g e n d i e u k h ie n (d r iv e r g e n e ) d o n g v a i tr o q u a n tr o n g s d n g h i e n c u u t r o n g n u d e v a tr e n t h e g i d i n h u n g h ie n c u u c u a C C h a tte r je e v a c s ( ) [ ] tr e n b e n h n h a n d K o lk a t a m i e n d o n g A n D o c h o t h a y t y l e d o t b ie n g e n D a n g d o t b i e n t h u d n g g a p n h a t tr e n EGFR EGFR la 3 % ( ,4 % ) K e t q u a n a y k h a c b i e t v d i k e t q u a n g h i e n c u u c u a ta c g i a M a i T r o n g K h o a v a c s ( 2 ) [ ] , tr o n g s d b e n h n h a n V ie t N a m d u p e x e t n g h i e m , t y l e d o t b ie n tr o n g v i e c lu a c h o n t h u o c T K I C a c d a n g d o t b i e n tr e n EGFR d exon c h i e m t y l e c a o n h a t, d u n g t h u la d o t b ie n L 8 R ta i e x o n T h e o n g h ie n c u u c u a P h a m T h j M a i v a c s ( 2 ) [ ] tr e n b e n h n h a n U T P b i e u m o t u y e n , d o t b i e n x a y c h u y e u d e x o n v a , v d i t y l e la n lu p t la ,8 v a ,6 % S u c h e n h le c h n a y c d th e d o n g h ie n c u u c u a c h u n g to i c d c d m a u c o n h a n c h e , ta p tr u n g c h u y e u v a o n h u n g b e n h n h a n d u p e c h a n d o a n d g ia i d o a n m u o n ( I I I - I V ) n e n c d t h e k h o n g p h a n a n h s u p h a n b o d a n g d o t b i e n c u a b e n h n h a n U T P K T B N d a n g d g ia i d o a n u n g th u sd m EGFR n h u L 8 R v a m a t d o a n e x o n c u n g v d i m o t s d d o t b ie n tr e n g e n k h a c n h u la L 8 R tren e x o n ( ,5 % ) , s a u d o la d o t b i e n m a t d o a n tr e n e x o n 19 KRAS BRAF d u p e p h a t h ie n c h ie m % , b a o g o m d a n g V 0 E v a G V B R A F -V 0 E , A L K -E M L la n h u n g d o t b ie n g e n k ic h h o a t v a d u p e c h u n g m i n h t in h n h a y c a m v d i c a c t h u o c T K I d a c d s a n tr e n la m s a n g [ , ] , N g h i e n c u u c u a c h u n g t o i c h o th a y , % ( t r u d n g h o p ) t r o n g t o n g sd b e n h n h a n t h a m g i a n g h i e n c u u m a n g m o t tr o n g n h u n g d o t b i e n n a y n e n c o th e c o t i e n l u p n g t o t h o n k h i d i e u tri c a c th u d e d ic h K d t q u a n a y c u n g t u o n g t u n h u n g h i e n c u u c u a H A T D a n g v a c s ( 2 ) P h a t h i e n ,7 % b e n h n h a n m a n g d o t b i e n n h a y T K I N g u p c la i , c a c d o t b i e n k h a n g t h u o c n h u T M h a y t h e m d o a n tr e n e x o n tr e n EGFR khO ng gap tr o n g n g h i e n c u u n a y C a c T K I t h e h e t h u n h a t la g e f i t in i b v a e r lo t in ib c d h o a t tin h u c c h e c h o n l o c c a o v a la d i e u tri d a u ta y c h o b e n h n h a n U T P K T B N m a n g d o t b ie n EGFR n h ay cam [ ] T h u n g h i e m la m s a n g F L A U R A s o s a n h h ie u q u a d ie u tri c u a o s i m e r t i n ib - T K l th e h e v d i g e n f i t in i b h o a c e r lo t in ib la d o t b i e n g e n c d t a n s u a t c a o t h u d U T P K T B N tr o n g U T P K T B N c d d o t b id n EGFR c h u a t u n g d i e u tri d a