Mishonga inoshandisa ropa inoshandisa ropa-kwete chirwere chemuviri-kuongorora kenza
Kazhinji, zvipembenene zvinoongororwa uchishandisa biopsies yemaviri. Chinyorwa chiduku chinotorwa kubva mumarara uye genotyped, kana kuongororwa nokuda kwemajini. Dambudziko nenzira iyi ndeyokuti zvipembenene zvinotyisa zvinogona kunge zvakaoma. Uyezve, chirwere chinoputika chinopa chete chidimbu chemuviri.
Kunyora mu Discovery Medicine muna 2015, Labgaa uye vanyori vanyori vanotaura zvinotevera pamusoro pezvakagadzirwa zvepabonde biopsy:
Nokuda kwezvikonzero zviri pachena, zvakaoma kutarisa tumarara yekushanduka nekugadzirisa biopsies. Uyewo, biopsy inongovhenekera nzvimbo imwe chete yechirwere uye naizvozvo haigoni kuratidzira mitezo yese yekuchinja mumatumbu makuru. Imwe nzira ingadai iri yekuwana zvidimbu zvakawanda zvechirwere chimwechete, asi sarudzo iyi inenge isiri yakakosha kana yakarurama.
Mvura inoputira inosanganisira kuenzana kwekuita DNA (ctDNA) uye zvimwe zvinokonzera mishonga muropa samples inowanikwa kuvarwere vane kenza. Iyi inowanzoonekwa yekufungidzira nzira inopikira kukurumidza, isingaiti, uye inodhura.
Nhoroondo yeMvura Yakasvibiswa
Muna 1948, Mandel naMetais, vaviri vevatsvakurudzi veFrance vakatanga kutanga vakawana ctDNA muropa revanhu vane utano hwakanaka. Uku kuwanikwa kwaiva mberi kwekanguva, uye hazvina kusvika makumi emakore gare gare ctDNA yakanga ichitaridzirwa zvakare.
Muna 1977, Leon uye avo vaishanda navo vakatanga kuwedzera yakawandisa yeCtDNA muropa rekenza varwere.
Pakazosvika 1989, Stroun uye vashandi vakawana neoplastic (kureva, kenza) muropa. Mushure mekunge izvi zvawanikwa, mamwe mapoka mazita akacherechedza kuchinja kwemuviri mumarara suppressors uye oncogenes, kusagadzikana kwema microsatellite, uye DNA methylation, iyo yakaratidza kuti ctDNA inosunungurwa pakuparadzirwa nemakumbo.
Kunyangwe tichiziva kuti ctDNA inobva mumasero emuviri inopararira muropa, mavambo, chiyero chekusunungurwa, uye nzira yekubudiswa kweDNA iyi haisati yajeka, nekutsvakurudza kunobvisa migumisiro inopesana. Imwe tsvakurudzo inoratidza kuti mamwe maronda anouraya ane mamwe maitiro echetere akafa uye anosunungura mamwe ctDNA. Zvisinei, kumwe kutsvakurudza kunoratidza kuti masero ose anosunungura ctDNA. Kunyange zvakadaro, zvinoratidzika sokuti maronda anokonzera kukonzera akasununguka mazinga eCtDNA muropa, zvichiita ctDNA chinhu chinonzi biomarker chekenza.
Nemhaka yekuparadzanisa kwakanyanya uye kuderera zvakanyanya muropa, ctDNA yakaoma kuparadzanisa nekuongorora. Pane kusiyanisa kweCtNA maitiro pakati peSerum uye plasma samples. Zvinoratidzika kuti serum yeropa panzvimbo pe plasma yeropa ndiyo inonyanya kukosha yeCtNA. Mukudzidza kwakaitwa naUmetani uye pamwe chete navo, ctDNA yakawanikwa yakanyanya kuderera mu plasma yakaenzaniswa neserum nekuda kwekukwanisa kurasikirwa kweDNA panguva yekucheneswa, sezvo kubatana uye mamwe mapuroteni ari kubviswa panguva yekugadzirira.
Maererano naHeitzer uye vashandi pamwe chete navo, pano pane dzimwe nyaya dzinoda kugadziriswa kuti dzigadzire zvinogona kuongororwa zve ctDNA:
Kutanga, preanalytical nzira dzinofanira kuve yakarongedzwa .... Kusarudzwa kwenzira yekuzviparadzanisa iyo inoita kuti kuwedzerwa kwehuwandu hwakawanda hweDNA yakakosha kunokosha uye yakaratidzwa kuti preanalytical zvinhu zvekutevedzera ropa uye kushandiswa zvinogona kukanganisa DNA chibereko .... Chechipiri, chimwe chezvinhu zvinonyanya kukosha ndekushaikwa kwekubatanidza nzira dzequantification. Kusiyanisa nzira dzekuita, ... kubudisa mhinduro dzakasiyana nokuti izvi zviyero zvinotaridzika zvachose kana kuti DNA chete inogadziriswa .... Chechitatu, zvishoma zvinonyatsozivikanwa nezvekwakabva uye kunyatsorongeka kweCtDNA kusunungurwa, uye mune zvidzidzo zvakawanda zvinokanganisa zviitiko zvinogonawo kuita kuti kusunungurwa kweCtNA.
Targeted vs. Untargeted Approaches
Parizvino, kune nzira mbiri dzinotorwa painoongorora plasma yeropa (kana serum) yeCtNA. Nzira yekutanga inotarirwa uye inotarisa zvakananga kuchinja kwemashoko anoratidza zvirwere. Nzira yechipiri isingatarisirwi uye inosanganisira kuongorora kwemajeni-yakawanda kutarisa ctDNA inoratidza kufanana nekenza. Zvimwewo, kuenzanisa kusarudzwa kwave kushandiswa seine mari yakawanda-inoshanda, nzira isingatarisirwi. Imba ndiyo zvikamu zveDNA zvakanyorwa kuti zviite mapuroteni.
Nezvinangwa zvinotarirwa, sarum inoongororwa nokuda kwekuzivikanwa kwechimiro chekuchinja mumutambo muduku wekuchinja kwekutyaira.
Kuchinja kwemotokari kunoreva kuchinja kwema genome kunokurudzira, kana "kuendesa," kukura kwekenza masero. Izvi zvinosanganisira mutauro weKRAS kana EGFR .
Nokuda kwekufambira mberi kwekombiji mumakore achangobva kupfuura, nzira dzakananga dzekuongorora kwema genome nokuda kwechidiki chectDNA dzakagoneka. Iyi inyanzvi inosanganisira ARMS (kukurudzira refractory mutation system); digital PCR (dPCR); mabhesi, emulsions, amplification, uye magnetics (BEAMing); uye kukwirira kwakadzika (CAPP-Seq).
Kunyange zvazvo kune huri kubudirira mune teknolojia iyo inoita kuti nzira yakatarwa ioneke, zvinongororwa zvinongoratidzwa chete zvinoshandiswa zvikamu zvishomanana zvemasimba (hotspots) uye inoshaya zvakawanda zvekuchinja kwechifambiro sechirwere chinodzvinyirira gemu.
Kubatsira kukuru kwemaitiro asingatarisirwi emvura yakasvibirira ndeyekuti inogona kushandiswa kune varwere vose nekuda kwekuti muedzo hauna kuvimba nezvakawanda zvemajeni ekuchinja. Kudzokorora kwemajini maitiro hazvifukidze mapepa ose uye haisi mazita ekurapa kenza. Kunyange zvakadaro, nzira iyi haina kukwanisa kunzwisisa nekunyatsonzwisisa uye kuongorora kwakakwana kwemarome genomes hazvikwanisi.
Nenzira, mutengo wekutsvaga gome rose yakanyanyisa. Muna 2006, mutengo wekutsvaga genome yose yaive madhora mazana matatu ($ 300,000 (USD). Pakazosvika gore ra2017, mutengo wakanga wakaderera kusvika madhora mazana maviri (USD) pamagenome, kusanganisira reagents uye kuunganidza maitiro ekugadzirisa mishonga.
Clinical Use of Liquid Biopsy
Kuedza kwekutanga kushandisa ctDNA kwaive kuongororwa uye kuenzanisa mazinga muvarwere vane utano neavo vanorwara nekenza kana avo vane chirwere chinorwara. Migumisiro yemabasa aya akabatanidzwa, uye zvimwe zvidzidzo zvinoratidza kusiyana kukuru kunoratidza chirwere, chirwere chisina zvirwere, kana kudzoka zvakare.
Chikonzero nei ctDNA inogona kushandiswa nguva imwe chete yekuongorora chirwere ndeyekuti zviyero zvakasiyana zveCtNA zvakabva mumaronda. Hasi mapundu ose "akadurura" DNA yakafanana. Muzvizhinji, zvakanyanya kufambisa, zvipembenene zvakapararira zvakadurura DNA yakawanda mumaparidziro kupfuura epakutanga, nzvimbo, mahara. Uyezve, kusiyana kwakasiyana-siyana kwemakumbo kunokonzera zvakasiyana-siyana zveDNA mumusangano. Chikamu chiduku chekuendesa DNA chinotorwa kubva mumarara chinowanzosiyana-siyana kune zvidzidzo uye mhando dzekenza, kubva kubva ku 0.01 kusvika ku 93%. Zvakakosha kucherechedza kuti, kazhinji, kechidiki chectDNA chinobva mudambudziko, iyo yose yakabva kune yakasvibirira mishonga.
Kupararira DNA kunogona kushandiswa senzira yekufananidzira yezvirwere. Kupararira DNA kunogona kushandiswa kuongorora kuchinja kwekenza munguva. Semuenzaniso, kumwe kuongorora kwakaratidza kuti makore maviri ekupukunyuka kwevaviri vane varwere vane kenza yakawanda (kureva, nhamba yevarwere vachiri vapenyu makore maviri mushure mekunge vaongororwa nekodharaal kanzira) uye KRAS hotspot mutations yaiva 100 muzana kune avo vasina uchapupu hwe DNA inotenderera inoenderana. Uyezve, zvinogoneka kuti mune ramangwana rakapfuura, kupararira DNA kunogona kushandiswa kutarisa zvipembenene zvakasimba.
Kupararira DNA kunogona kushandiswawo kuongorora kupindura kwerapi. Nemhaka yokuti kuendesa DNA zvinyorwa zviri nani zviri nani zvemajeni ekugadzira tumarara, iyi DNA inogona kunge ine DNA inosarudzwa, iyo inogona kushandiswa pane kutsvaga DNA inowanikwa kubva mumakumbo pachavo.
Iye zvino, ngatitarisei mimwe mienzaniso chaiyo yezvinyorwa zvemvura.
Guardant360
Muchengetedzi Utano hwakagadzirisa muedzo unoshandisa chizvarwa chinotevera chichienzanidza nehuwandu hwepachirongwa cheDNA chekuchinja uye kromosomal rearrangements yemarome anokonzerwa nekenza 73. Muchengeti Wehutano akabudisa purogiramu yekuongorora kushandiswa kwemvura inoshandiswa mumvura inocology. Chidzidzo chacho chakashandisa sampu yeropa kubva kuvarwere vane 15 000 vane pamwe chete 50 tumor types.
Pamusoro pezvikamu zvizhinji, zvinogumuchirwa nemvura inonzi biopsy test inowirirana nemararamiro emagetsi anoonekwa mumavhiramu emhuka.
Maererano neNIH:
Guardant360 yakaratidza kuchinja kwakafanana kwakakonzerwa nemakemikari ane chokuita nekenza seEGFR, BRAF, KRAS , uye PIK3CA pamagariro akafanana neaya ainge aonekwa mumatomu anokonzera matumbo, inotarisana ne 94% kusvika 99%.
Uyezve, maererano neNIH vatsvakurudzi vakarondedzera zvinotevera:
Mune chikamu chechipiri chekudzidza, vatsvakurudzi vakaongorora varwere vanosvika 400-vazhinji vavo vaiva nemapapu kana kenza yakaoma-avo vaiva neropa reCtNA uye tumor tissue tissue DNA yakawanikwa uye yakafananidza maitiro ezvakaita genomic. Kururamisa kwakakwana kwechidimbu chemvura inofananidzwa nemigumisiro inobva mumarara inonzi biopsy analyzes yaiva 87%. Kururama kwakawedzera kusvikira 98% apo ropa uye sampuli zvinyorwa zvakaunganidzwa mukati memwedzi mitanhatu kubva kune mumwe.
Guardant360 yakanga yakarurama kunyange zvazvo maitiro ekupararira DNA muropa akanga akaderera. Kazhinji, kupararira DNA yakakonzerwa chete kunoumba 0.4 muzana yeDNA muropa.
Kakawanda, achishandisa mvura yakasvibiswa, varindi vatsvakurudzi vakakwanisa kuziva zvirwere zvinotapira zvinogona kutungamirira kurapwa navanachiremba mu 67 muzana yevarwere. Ava varwere vaikodzera kugadziriswa kweDWA-pamwe nemishonga yekuongorora.
ctDNA uye Lung Cancer
Muna 2016, FDA yakabvumira cobas EGFR Mutation Test kuti ishandiswe pakuonekwa kweEGFR mutations muDNA inopararira yevarwere vane kenza yemapapu. Uyu muedzo waiva wekutanga FDA-inogamuchirwa mvura ye-biopsy uye akacherechedza varwere vanogona kunge vari kunyoreswa kurapwa nemishonga inotarisirwa vachishandisa erlotinib (Tarceva), afatinib (Gilotrif), uye gefitinib (Iressa) sokurapa kwekutanga, uye osimeritinib (Tagrisso) se yechipiri-linerapa kurapwa. Izvi zvinotarisirwa maitiro ekurwisa masero emukenza nemamwe matanho eEGFR .
Zvinonyanya kukosha, nekuda kwenhamba yakawanda yemigumisiro yakaipa-yakaipa, FDA inokurudzira kuti mhando yemuviri inoshandiswa zvakare inotorwa kubva kune murwere ane chinokonzera mvura yakashata.
ctDNA uye Liver Cancer
Nhamba yevanhu vanofa nekenza yeropa yakakura mumakore makumi maviri adarika. Pari zvino, kenza yemuropa ndiyo yechipiri inokonzera kukonzera rufu mupasi. Hakuchina mazai akanaka anowanikwa kuti aone nekuongorora chiropa, kana hepatocellular (HCC), kenza. Kupararira DNA kunogona kunge iri bhiomarker yakanaka yekenza yeropa.
Funga nezvemashoko akatevera anobva kuLagbaa uye vanyori-vanyori pamusoro pekugona kushandisa DNA kuongorora kenza yechiropa:
Hypermethylation yaRASSF1A, p15, uye p16 yakarondedzerwa semashandisi ekuongorora zviratidzo munguva yekudzidza zvakarezve kusanganisira 50 HCC varwere. Chiratidzo chechina chemajini (APC, GSTP1, RASSF1A, uye SFRP1) chakaedzwawo kuti chiongororwe, apo methylation yeRASSF1A yakashumirwa sehuwandu hwechirevo. Zvimwe zvidzidzo zvakatsvakurudza ctDNA muHCC varwere vachishandura inyanzvi yekugadzirisa inyanzvi .... Zvinotyisa, DNA yakawanda inoshandiswa nhamba idzi dzakawanikwa muvatakuri vaviri veHBV pasina nhoroondo yekare yeHCC munguva yekuunganidza ropa, asi ndiani akavaka HCC panguva yekutevera. Ichi chakawana chakazarura mukova wekuongorora kopi yenhamba kuchinjwa mu ctDNA sechinhu chekuongorora chekutanga kweHCC kuona.
Shoko Rinobva
Mishonga yezvinyorwa ndeye nzira itsva inonakidza yekuita genomic kuongorora. Parizvino, mamwe mabhiopsies emvura, ayo anopa mazamu akawanda ekufananidzira, anowanikwa kune vanachiremba kuti vatsigire ruzivo rwezvemagetsi anowanikwa kubva muhuputi hwemhuka. Iko kunewo mamwe majee emvura anokwanisa kushandiswa panzvimbo yezvinyorwa zvebiopsy-apo zvinyorwa zvebiopsies zvisingawanikwi.
Zvakakosha kuchengetedza mupfungwa kuti dzakawanda zvinoshandiswa mumvura zvinoshandiswa zvinowanzoitika uye zvimwe zvitsvakurudzo zvinoda kuitwa kune nyama kunze kwekushandiswa kwechirongwa chekupindira uku.
> Sources:
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> Heitzer E, Ulz P, Geigl JB. Kupararira Tumor DNA seAquid Biopsy for Cancer. Clinical Chemistry. 2015; 61: 112-123. doi: 10.1373 / kliniki.2014.222679
> Lagbaa J, Villanueva A. Liquid biopsy mukenza yeropa. Discovery Medicine. 2015; 19 (105): 263-73.
> Mishonga Inoputi: Kushandisa DNA muRopa Kuona, Teerera, uye Kurapa Kansa. NIH.
> Umetani N, et al. Nhamba yakakwirira yekusununguka kweDNA muSerum muparum asi haisati yakonzerwa neDNA yakasvibiswa panguva yakaparadzana. Ann NY Academy Sci. 2006; 1075: 299-307.
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