amakuru

Mu myaka icumi ishize, tekinoroji ikurikirana ya gene yakoreshejwe cyane mu bushakashatsi bwa kanseri no mu mavuriro, iba igikoresho gikomeye cyo kwerekana ibimenyetso bya kanseri biranga kanseri. Iterambere mu gusuzuma indwara ya molekuline hamwe nubuvuzi bugamije iterambere ryateje imbere iterambere ryibibyimba bivura neza kandi bizana impinduka nini mubice byose byo gusuzuma no kuvura ibibyimba. Kwipimisha genetike birashobora gukoreshwa mukuburira ibyago bya kanseri, kuyobora ibyemezo byo kuvura no gusuzuma ibizaba, kandi nigikoresho cyingenzi mugutezimbere ivuriro ry’abarwayi. Hano, turagaragaza muri make ingingo ziherutse gusohoka muri CA Kanseri J Clin, JCO, Ann Oncol nibindi binyamakuru kugirango dusuzume ikoreshwa ryipimisha geneti mugupima kanseri no kuvura.

Guhinduka kwa somatike na mutation ya germine. Muri rusange, kanseri iterwa na ADN ihindagurika ishobora kuragwa n'ababyeyi (mutation ya germine) cyangwa ikagerwaho n'imyaka (mutation somatike). Imihindagurikire y’imiterere y’imiterere iboneka kuva akivuka, kandi mutator ubusanzwe itwara ihinduka ryimiterere muri ADN ya buri selile yo mumubiri kandi irashobora kwanduzwa urubyaro. Guhinduka kwa somatike bigerwaho nabantu mumasoko adakina kandi mubisanzwe ntabwo bihabwa urubyaro. Imiterere ya germine na somatike irashobora gusenya ibikorwa bisanzwe byimikorere ya selile kandi biganisha kumihindagurikire mibi ya selile. Guhinduka kwa somatike ni moteri yingenzi ya malignance na biomarker ihanura cyane muri oncology; icyakora, abagera kuri 10 kugeza kuri 20 ku ijana by'abarwayi b'ibibyimba bitwara ihindagurika rya mikorobe ryongera cyane kanseri yabo, kandi zimwe muri izo ihinduka nazo zivura.
Guhindura ibinyabiziga no guhindura abagenzi. Ntabwo ADN zose zihindura imikorere yimikorere; ugereranije, bisaba ibintu bitanu kugeza ku icumi byabayeho, bizwi nka “mutation mutation,” kugirango bitume selile zangirika. Guhindura abashoferi bikunze kugaragara muri gen zifitanye isano cyane nibikorwa byubuzima bwakagari, nka gen zigira uruhare mukugenzura imikurire yimikorere, gusana ADN, kugenzura ingirabuzimafatizo nibindi bikorwa byubuzima, kandi bifite ubushobozi bwo gukoreshwa nkintego zo kuvura. Nyamara, umubare rusange w’imihindagurikire ya kanseri iyo ari yo yose ni nini cyane, kuva ku bihumbi bike muri kanseri zimwe na zimwe kugeza ku barenga 100.000 muri kanseri zimwe na zimwe zihindagurika cyane. Imihindagurikire myinshi idafite akamaro cyangwa ibinyabuzima bifite aho bihuriye, kabone niyo ihinduka ryabaye mu karere ka code, ibintu nkibi bidahinduka byitwa “mutation y'abagenzi”. Niba ubwoko bwa gene mubwoko runaka bwibibyimba bihanura igisubizo cyabwo cyangwa kurwanya imiti, variant ifatwa nkigikorwa cyubuvuzi.
Oncogène na genes suppressor genes. Imirasire ikunze guhinduka muri kanseri irashobora kugabanywamo ibice bibiri, oncogène na genes suppressor genes. Mu ngirabuzimafatizo zisanzwe, poroteyine yashizwemo na oncogène igira uruhare runini mu guteza imbere ikwirakwizwa ry'uturemangingo no guhagarika apoptose ya selile, mu gihe poroteyine yashizwemo na genoside ya oncosuppressor ishinzwe cyane cyane kugenzura nabi amacakubiri kugira ngo ikore imikorere isanzwe ya selile. Muburyo bwo guhindura ibintu nabi, ihinduka ryimiterere ya genomic riganisha ku kongera ibikorwa bya oncogene no kugabanuka cyangwa gutakaza ibikorwa bya gene ya oncosuppressor.
Itandukaniro rito nuburyo butandukanye. Ubu ni ubwoko bubiri bwingenzi bwimiterere muri genome. Impinduka nto zihindura ADN muguhindura, gusiba, cyangwa kongeramo umubare muto wibanze, harimo kwinjiza shingiro, gusiba, gushushanya, gutangira gutakaza codon, guhagarika ihindagurika rya codon, nibindi. Guhindura imiterere ni genome nini ihindagurika, irimo ibice bya gene bifite ubunini kuva mubihumbi bike kugeza kuri chromosome, gusiba kwa chromosome, gusiba, kwigana, Ihinduka rishobora gutera kugabanuka cyangwa kuzamura imikorere ya poroteyine. Usibye impinduka kurwego rwa genes kugiti cye, imikono ya genomic nayo iri muri raporo zikurikirana. Imikono ya genomic irashobora kugaragara nkuburyo bugoye bwo gutandukana guto na / cyangwa imiterere, harimo umutwaro uhindagurika wibibyimba (TMB), ihungabana rya microsatellite (MSI), nubusembwa bwa homologique.

Guhinduranya kwa clone na mutation ya subclonal. Imihindagurikire ya clone iboneka mu ngirabuzimafatizo zose, zirahari mugupima, kandi zigakomeza kuboneka nyuma yo kuvura. Kubwibyo, ihinduka ryimiterere ya clone rifite ubushobozi bwo gukoreshwa nkintego zo kuvura ibibyimba. Guhindagurika kwa subclonal biboneka mugice gito cya selile ya kanseri kandi birashobora kumenyekana mugitangira kwisuzumisha, ariko bikabura hamwe nibisubiramo nyuma cyangwa bikagaragara nyuma yo kuvurwa. Kanseri itandukanye bivuga ko habaho ihinduka ryinshi ryimiterere ya kanseri imwe. Ikigaragara ni uko umubare munini w’imiterere ihindagurika ry’abashoferi mu moko yose asanzwe ya kanseri ari ihinduka ry’imiterere kandi rikomeza guhagarara neza muri kanseri. Kurwanya, bikunze guhuzwa na subclone, ntibishobora kuboneka mugihe cyo kwisuzumisha ariko bikagaragara iyo bisubiye nyuma yo kuvurwa.

Tekiniki gakondo AMAFI cyangwa selile karyotype ikoreshwa mugutahura impinduka kurwego rwa chromosomal. AMAFI arashobora gukoreshwa mugutahura gene, gusiba, no kongera imbaraga, kandi bifatwa nk "" urwego rwa zahabu "rwo gutahura izo variant, hamwe nukuri kandi gukomeye ariko kwinjiza bike. Indwara zimwe na zimwe ziterwa na hematologique, cyane cyane leukemia ikaze, karyotyping iracyakoreshwa mu kuyobora indwara no gusuzuma, ariko ubu buhanga bugenda busimburwa buhoro buhoro hifashishijwe intego ya molekile nka FISH, WGS, na NGS.
Impinduka muri genes zitandukanye zirashobora gutahurwa na PCR, haba mugihe nyacyo PCR na PCR igabanuka. Ubu buhanga bufite sensibilité nyinshi, burakwiriye cyane cyane gutahura no kugenzura ibikomere bito bisigaye, kandi birashobora kubona ibisubizo mugihe gito ugereranije, imbogamizi nuko urwego rwo gutahura ari ruto (mubisanzwe gusa hamenyekana ihinduka ryimiterere ya gen imwe cyangwa nkeya), kandi ubushobozi bwo gupima byinshi ni buke.
Immunohistochemie (IHC) nigikoresho cyo kugenzura poroteyine gikunze gukoreshwa mu kumenya imvugo y’ibinyabuzima nka ERBB2 (HER2) hamwe na resitora ya estrogene. IHC irashobora kandi gukoreshwa mugutahura poroteyine zihariye zahinduwe (nka BRAF V600E) hamwe na gene yihariye (nka ALK fusion). Ibyiza bya IHC nuko ishobora kwinjizwa byoroshye mubikorwa bisanzwe byo gusesengura ibice, bityo irashobora guhuzwa nibindi bizamini. Mubyongeyeho, IHC irashobora gutanga amakuru kubyerekeranye na proteine ​​ya subcellular. Ibibi ni ubunini buke kandi busabwa gahunda nyinshi.
Urukurikirane rwibisekuru bya kabiri (NGS) NGS ikoresha tekinoroji yo hejuru ikoresheje uburyo bukurikiranye kugirango ibone itandukaniro kurwego rwa ADN na / cyangwa RNA. Ubu buhanga bushobora gukoreshwa mugukurikirana genome yose (WGS) hamwe nakarere ka gene gashimishije. WGS itanga amakuru arambuye ya mutation ya genomic, ariko hariho inzitizi nyinshi zibangamira ikoreshwa ryamavuriro, harimo no gukenera ingirabuzimafatizo nshya (WGS ntikibereye gusesengura ingero za foromine-immobilizasiyo) hamwe nigiciro kinini.
Intego za NGS zikurikirana zirimo exon zose zikurikirana hamwe nintego ya gen. Ibi bizamini bikungahaza uturere dushimishijwe nubushakashatsi bwa ADN cyangwa amplification ya PCR, bityo bikagabanya ingano yikurikiranya risabwa (exome yose igizwe na 1 kugeza kuri 2 ku ijana bya genome, ndetse na panne nini irimo genes 500 zigizwe na 0.1% bya genome gusa). Nubwo gahunda ya exon yose ikora neza mubice bya fermine-byagenwe, igiciro cyacyo gikomeza kuba kinini. Intego ya gene ihuriweho nubukungu kandi yemerera guhinduka muguhitamo genes zipimwa. Byongeye kandi, gukwirakwiza ADN yubuntu (cfDNA) bigenda bigaragara nkuburyo bushya bwo gusesengura genomique y’abarwayi ba kanseri, izwi ku izina rya biopies. Ingirabuzimafatizo za kanseri n'uturemangingo dusanzwe birashobora kurekura ADN mu maraso, kandi ADN yavuye mu ngirabuzimafatizo ya kanseri yitwa kuzenguruka ibibyimba ADN (ctDNA), bishobora gusesengurwa kugira ngo hamenyekane ihinduka ry’imihindagurikire y'uturemangingo.
Guhitamo ikizamini biterwa nikibazo cyihariye cyamavuriro agomba gukemurwa. Byinshi mubinyabuzima bifitanye isano nubuvuzi bwemewe birashobora gutahurwa nubuhanga bwa FISH, IHC, na PCR. Ubu buryo bufite ishingiro kugirango hamenyekane bike bya biomarkers, ariko ntibishobora kunoza imikorere yo gutahura hamwe no kongera ibicuruzwa, kandi niba hagaragaye ibimenyetso byinshi bya biomarkers, hashobora kuba hatariho tissue zihagije zo gutahura. Muri kanseri zimwe na zimwe, nka kanseri y'ibihaha, aho ingero za tissue zigoye kubona kandi hariho biomarkers nyinshi zo kwipimisha, gukoresha NGS ni amahitamo meza. Mu gusoza, guhitamo ibizamini biterwa numubare wa biomarkers ugomba gupimwa kuri buri murwayi n'umubare w'abarwayi bapimwa biomarker. Rimwe na rimwe, gukoresha IHC / FISH birahagije, cyane cyane iyo hagaragaye intego, nko kumenya imiti ya estrogene, reseptor progesterone, na ERBB2 ku barwayi ba kanseri y'ibere. Niba hakenewe ubushakashatsi bwimbitse ku ihindagurika ry’imiterere no gushakisha intego zishobora kuvurwa, NGS irateguwe kandi ihendutse. Mubyongeyeho, NGS irashobora gusuzumwa mugihe ibisubizo bya IHC / FISH bidasobanutse cyangwa bidasobanutse ..

Amabwiriza atandukanye atanga umurongo ngenderwaho abarwayi bagomba kwemererwa kwipimisha. Mu mwaka wa 2020, Itsinda ry’imirimo ya ESMO Precision Medicine ryatanze ibyifuzo bya mbere byo gupima NGS ku barwayi barwaye kanseri yateye imbere, risaba ko buri gihe hasuzumwa NGS ku barwayi ba kanseri y'ibihaha yateye imbere idafite kanseri, kanseri ya prostate, kanseri y'amara, kanseri y'ibyondo, na kanseri y'intanga ngore, kandi mu 2024, ESMO yavuguruye hashingiwe kuri ibyo, isaba ko hashyirwaho kanseri y'ibere ndetse n'ibibyimba bidasanzwe. Nkibibyimba bya gastrointestinal tromal, sarcomas, kanseri ya tiroyide na kanseri zinkomoko itazwi.
Mu 2022, Igitekerezo cya Clinique ya ASCO ku gupima genome ya somatike ku barwayi barwaye kanseri metastatike cyangwa yateye imbere ivuga ko niba imiti ifitanye isano na biomarker yemewe ku barwayi bafite ibibyimba bikomeye cyangwa byateye imbere, birasabwa kwipimisha ku barwayi. Kurugero, kwipimisha genomic bigomba gukorwa kubarwayi barwaye melanoma metastatike kugirango berekane ihinduka rya BRAF V600E, kuko RAF na MEK inhibitor zemewe kuri iki kimenyetso. Byongeye kandi, ibizamini bya geneti bigomba no gukorwa niba hari ikimenyetso kigaragara cyo kurwanya imiti ihabwa umurwayi. Urugero, Egfrmab ntacyo ikora muri KRAS mutant kanseri yibara. Mugihe harebwa niba umurwayi akwiranye na gene ikurikirana, imiterere yumubiri wumurwayi, ibitera, hamwe nicyiciro cyibibyimba bigomba guhuzwa, kuko urukurikirane rwintambwe zisabwa kugirango hakurikiranwe genome, harimo uruhushya rw’abarwayi, gutunganya laboratoire, no gusesengura ibisubizo bikurikirana, bisaba umurwayi kugira ubushobozi buhagije bwumubiri ndetse nigihe cyo kubaho.
Usibye ihinduka rya somatike, kanseri zimwe na zimwe zigomba no gupimwa ingirabuzimafatizo. Kwipimisha ihinduka ryimiterere ya mikorobe birashobora guhindura ibyemezo byo kuvura kanseri nka BRCA1 na BRCA2 ihinduka mumabere, intanga ngore, prostate, na kanseri yandura. Guhindagurika kwa Germline birashobora kandi kugira ingaruka mugupima kanseri no gukumira abarwayi. Abarwayi bashobora kwipimisha ihindagurika rya mikorobe bakeneye kubahiriza ibintu bimwe na bimwe, birimo ibintu nkamateka yumuryango wa kanseri, imyaka yo kwisuzumisha, nubwoko bwa kanseri. Nyamara, abarwayi benshi (bagera kuri 50%) bitwaje ihinduka ry’imiterere y’imiterere ya mikorobe ntibujuje ibipimo gakondo byo gupima ihinduka ry’imiterere ya mikorobe ishingiye ku mateka y’umuryango. Kubera iyo mpamvu, kugira ngo hamenyekane neza abatwara mutation, Ikigo cy’igihugu gishinzwe kurwanya kanseri (NCCN) kirasaba ko abarwayi bose cyangwa benshi barwaye amabere, intanga ngore, endometrale, pancreatic, colorectal, cyangwa prostate bapimwa ihinduka ry’imiterere ya mikorobe.
Ku bijyanye n’igihe cyo kwipimisha geneti, kubera ko umubare munini w’imihindagurikire y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere ya kanseri, birakwiriye ko hakorwa ibizamini bya geneti ku barwayi mu gihe cyo gusuzuma kanseri yateye imbere. Kwipimisha genetike yakurikiyeho, cyane cyane nyuma yubuvuzi bwa molekuline, kwipimisha ctDNA nibyiza kuruta ADN yumubiri wibibyimba, kubera ko ADN yamaraso ishobora kuba irimo ADN ivuye mubikomere byose, bikaba byiza cyane kubona amakuru ajyanye na heterogeneité yibibyimba.
Isesengura rya ctDNA nyuma yo kuvurwa rishobora guhanura ibibyimba bivura no kuvura indwara hakiri kare kuruta uburyo busanzwe bwo gufata amashusho. Nyamara, protocole yo gukoresha aya makuru kugirango ayobore ibyemezo byo kuvura ntabwo yashyizweho, kandi isesengura rya ctDNA ntirisabwa keretse mugihe cyibizamini byo kwa muganga. ctDNA irashobora kandi gukoreshwa mugusuzuma ibikomere bito bisigaye nyuma yo kubagwa ibibyimba bikabije. kwipimisha ctDNA nyuma yo kubagwa ni guhanura gukomeye kwindwara zikurikira kandi birashobora gufasha kumenya niba umurwayi azungukirwa na chimiotherapie yongeyeho, ariko biracyasabwa gukoresha ctDNA hanze y ibizamini byubuvuzi kugirango bayobore ibyemezo bya chimiotherapie.

Gutunganya amakuru Intambwe yambere mugukurikirana genome nugukuramo ADN kuburugero rwabarwayi, gutegura amasomero, no kubyara amakuru akurikirana. Amakuru yibanze arasaba kurushaho gutunganywa, harimo gushungura amakuru yujuje ubuziranenge, kuyagereranya na genome yerekanwe, kumenya ubwoko butandukanye bwimihindagurikire binyuze muri algorithms zitandukanye zisesengura, kumenya ingaruka zibi byahinduwe mubisobanuro bya poroteyine, no gushungura umurongo wa mikorobe.
Umushoferi wa gene annotage yagenewe gutandukanya abashoferi nabagenzi. Guhindura ibinyabiziga biganisha ku gutakaza cyangwa kongera ibikorwa bya gene suppressor yibikorwa. Impinduka ntoya ziganisha ku kudakora kwa genes suppressor genes zirimo ihinduka ridafite ishingiro, ihinduka ryimiterere ihindagurika, hamwe nurufunguzo rwibanze rwa site, kimwe no gutangira gusiba codon, guhagarika gusiba codon, hamwe nubwinshi bwimikorere ya intron insertion / gusiba. Byongeye kandi, ihinduka rya missense hamwe na intron ntoya yinjizamo / gusiba birashobora kandi gutuma umuntu atakaza ibikorwa bya gene suppressor gene mugihe bigira ingaruka kumurongo wingenzi. Imiterere yuburyo buganisha ku gutakaza ibikorwa bya suppressor gene yibikorwa birimo gusiba gene igice cyangwa cyuzuye hamwe nibindi binyabuzima biganisha ku gusenya ikadiri yo gusoma. Impinduka ntoya ziganisha kumikorere ya oncogène zirimo ihinduka rya missense hamwe na rimwe na rimwe intron yinjizamo / gusiba bigamije poroteyine zingenzi zikora. Mubihe bidasanzwe, guhagarika poroteyine cyangwa gutera urubuga ihinduka bishobora gutuma ukora oncogène. Imiterere itandukanye iganisha kuri oncogene ikora harimo guhuza gene, gusiba gene, no kwigana gene.
Ibisobanuro bya Clinical of genomic variation isuzuma akamaro kivuriro ryimiterere ihindagurika, ni ukuvuga agaciro kabo ko gusuzuma, kumenyekanisha, cyangwa kuvura. Hariho ibimenyetso byinshi bishingiye kuri sisitemu yo gutanga amanota ashobora gukoreshwa mu kuyobora ibisobanuro bya clinique yo gutandukana kwa genomic.
Ububiko bw’Urwibutso rwa Sloan-Kettering Centre's Precision Medicine Oncology Database (OncoKB) ishyira ubwoko bwa gene mu nzego enye zishingiye ku gaciro kabo ko guhanura gukoresha: Urwego 1/2, rwemejwe na FDA, cyangwa amavuriro yemewe y’ibinyabuzima ateganya igisubizo cy’ibimenyetso byemewe ku biyobyabwenge byemewe; Urwego rwa 3, FDA yemewe cyangwa itemewe na biomarkers itangaza igisubizo cyibiyobyabwenge byibasiwe nubuvuzi bwerekanye amasezerano mubigeragezo byamavuriro, naho urwego rwa 4, biomarkers zitemewe na FDA ziteganya igisubizo cyibiyobyabwenge byibasiwe n’ibimenyetso byerekana ibimenyetso bifatika by’ibinyabuzima mu manza z’amavuriro. Itsinda rya gatanu rijyanye no kurwanya imiti ryongeyeho.
Sosiyete y'Abanyamerika ishinzwe indwara ya molecular (AMP) / Sosiyete y'Abanyamerika ya Clinical Oncology (ASCO) / Ishuri Rikuru ry’Abanyamerika b'Abanyamerika (CAP) amabwiriza yo gusobanura itandukaniro rya somatike igabanya itandukaniro rya somatike mu byiciro bine: Icyiciro cya mbere, gifite akamaro gakomeye mu mavuriro; Icyiciro cya II, gifite akamaro k’ubuvuzi; Icyiciro cya III, ibisobanuro byubuvuzi ntibizwi; Icyiciro cya IV, ntabwo kizwi ko gifite akamaro mubuvuzi. Gusa icyiciro cya I na II gusa bifite agaciro kubyemezo byo kuvura.
ESMO ya Molecular Target Clinical Operability Scale (ESCAT) ishyira ubwoko bwa gene mubice bitandatu: Urwego I, intego zibereye gukoreshwa bisanzwe; Icyiciro cya II, intego ikomeje kwigwa, birashoboka ko izakoreshwa mugupima abaturage barwayi bashobora kungukirwa nibiyobyabwenge, ariko hakenewe amakuru menshi kugirango abishyigikire. Icyiciro cya III, intego za gene zigaragaza inyungu zubuvuzi mubindi binyabuzima bya kanseri; Icyiciro cya IV, gusa intego za gen zigamije gushyigikirwa nibimenyetso bifatika; Mu cyiciro cya V, hari ibimenyetso bifatika byerekana akamaro k’ubuvuzi bwo kurwanya ihinduka ry’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y’imihindagurikire y'ikirere, Icyiciro cya X, kubura agaciro kivuriro.