
utparivartaniy swakshya

utparivartaniy swakshya yaa vishisht utparivartanachya prakriyanmadhun udbhavananya utparivartanachya prakaranche vaishishtyapurn sanyojan aahet, jase qee dii. aine. aii. pratikruti avishvas, bahya aanee antarjan genotoxin exposure, sadosh dii. aine. aii. durusti marg aanee dii. aine. aii. enzymatic editing.
hii sandnya done bhinn sankalpanansathi vaparali jaate, bahutekda ektrit kelee jaateh utparivartit swakshari aanee arbud swakshari. tyacha mool vapar, mutagen signature, prayogshalet dnyat myutejandware kelelya utparivartananchya namunyacha sandarbh deto aanee itar myutejandware tayar keela jaat nahee-manvi swakshari mhanoon mutagensathi adviteey, heey swaksharikartyasathi adviteey aahe. vishishtatemule peshichya utparivartananmadhun nantar utparivartanacha andaj lavala jaau shakato, haah vakyansh tumourchya prakarachya vaishishtyapurn utparivartananchya namunyacha sandarbh deto, jaree samanyatah tumourchya prakarasathi kinwa utparivartanasathi adviteey nasato. jarr tumour mutational signature eka adviteey mutagen mutational signatureshee julate, tarr rugnachya durchya bhootkalat jhalelya carcinogen exposure kinwa mutagenesis prakriyecha andaj lavane vaidh aahe. vadhatya pramanat parishkrut tumourchya swakshya mutagenchya swakshyansathi niyukt kelya jaat aahet.
karkarogatil utparivartaniy swakshya samajoon ghene heey carcinogenesis aanee samanya sharirik utparivartanat samavisht asalelya jaivik yantranebaddal antardrushti pradan karate. utparivartaniy swakshyanni karkarogavaril upchar aanee karkarog pratibandhat tyanchi upayuktata darshavili aahe. oncogenomicschya kshetratil pragatimule aanvik lakshyit upcharpaddhaticha vikas aanee vapar saksham jhaala aahe, parantu asha upcharpaddhati aitihasikdrushtya oncogenic chalakanna pratibandh karnyavar kendrit aahet (udaa.jee. "ii. jee. eff. aar."..................................................................................................................................................................................................................................................... agadi alikade, utparivartaniy swakshyache swarupankan heey oncological vyavasthapan aanee lakshyit upcharpaddhatinchya vaparas margadarshan karnyat yashasvi tharale aahe (udaa.jee. visangati durustimadhye immunotherapy vividh prakarchya karkarogachi kamatarata, samaroop punarsanyojan kamatarata asalelya stanachya karkarogamadhye krutrim pranghatakta vaparnyasathi platinum aanee parp avarodhak).
samanya sankalpana.
janukeey mahitee.
karkarogachya utparivartanatmak swakshya vishleshanasathi vishisht gathinche tumour utparivartan catalog (utparivartanache prakar aanee mojani) tayar karnyasathi karkarogachya genome sequencingmadhun jodidar-samanya dii. aine. aii. sequencings genomic deta aavashyak asato. vividh prakarche utparivartan (udaa.jee. karkarogamadhye utparivartaniy swakshyache pratirup tayar karnyasathi ekal nucleotide prakar, indell, sanrachanatmak prakar) vaiyaktikaritya kinwa sanyojanat vaparale jaau shakatat.
utparivartananche prakarah moolbhut paryay.
moolbhut paryayache sahaa varg aaheth c> a, c> g, c> t, t> a, t> c, t> g. jee> tii pratisthapan heey see> paryay samatulya manale jaate kaaran suruvatila konatya dna strandver (pudhe kinwa ulat) pratisthapan ghadale heey vegale karane shakya nahee. tyamule see> aii aanee jee> tii heey donhi paryay 'see> aii' vargacha bhag mhanoon mojale jaatat. yach karanastav, jee> see, jee> aii, aii> tii, aii> jee aanee aii> see utparivartan anukrame "see> jee", "see> tii", "tii> aii", "tii> see" aanee "tii> jee" vargancha bhag mhanoon mojale jaatat.
5 'aanee 3' chya shejaril payanpasoon mahitee ghetalyane (jyala parshvik aadhar jodya kinwa trinucleotide sandarbh dekhil mhanatat) 96 sambhavya utparivartanache prakar hotat (udaa.jee. a [c> a] a, a [c> a] t, ityadi.). tumourchi utparivartan soochi 96 utparivartan prakaranpaiki eka prakarat pratyek nucleotide prakarache (ess. aine. vhee.) (samanarthi shabdah bases-payer pratisthapan kinwa pratisthapan bindu utparivartan) vargikaran karoon aanee yaa 96 utparivartan prakaranpaiki pratyekasathi paryayanchi ekoon sankhya mojoon tayar kelee jaate (aakruti pahaa).
tumour utparivartan soochi.
 ekada utparivartan soochi (udaa.jee. gathichya 96 utparivartanachya prakaranpaiki pratyekasathi ganana kelee jaate), gathichya janukeey bhupradeshatil vegvegalya utparivartaniy swakshyanche yogdan samajoon ghenyasathi done marg aaheth
carcinogenesismadhye vividh utparivartaniy swakshyanche yogdan olakhane heey arbud jivashastrabaddal antardrushti pradan karate aanee lakshit upcharansathi sandhee deu shakate.
utparivartananche prakarah indels.
signature 3, jeey samaroop punarsanyojan (etch. aar.) kamatarata gatheet disate, teey mothya indelchya (50 nucleotidesparyant) vadhiv bharasah breakpointswar ativyapi sookshm homologieshy sambandhit aahe. asha gathimadhye, dii. aine. aii. double-strand breakchi durusti uchch nishtha etch. aar. durustiaivaji naun-homologous end joining (aine. etch. eae. jeey.) kinwa microhomology-madhyasth end joining (emm. emm. eae. jeey.) chya achook durusti yantranedvare kelee jaate.
sookshm upgrah asthiratechya gathimadhye disana signature 6 madhye, nucleotide punaravrutti honanya bhagat 1 bii. pii. indelche sanwardhan dekhil disun yete.
utparivartananche prakarah sanrachanatmak prakar.
samaroop punarsanyojan kamataratemule signature 3 pratisthapan namuna tayar hoto, parantu sanrachanatmak prakaranche oze dekhil vadhate. samaroop punarsanyojan naan jhalyas, samaroop nasalela shevat jodanyamule gunasutranche sthanantar, gunasutranche vyutkram aanee prati sankhya prakar yasarkhya mothya sanrachanatmak prakaranna chalana milate.
utparivartaniy swakshya.
vayashi sambandhit utparivartan.
aine. pii. [see> tii] jee trinucleotide sandarbhat sii> tii sankraman (anuvanshiki) chey varchasva signature 1 madhye darshavile aahe aanee karkarogachya nidanachya velee rugnachya vayashi sambandhit aahe. 5-methylcytocene utsfurt nirmitikaran hii antarnihit prastavit jaivik yantrana aahe.
signature 5 madhye transcriptional strand bices aii. pii. tii. pii. aine. trinucleotide sandarbhat tii> see badalanche varchasva aahe.
samaroop punarsanyojan kamatarata.
signature 3 anek utparivartan varganchya uchch utparivartananchi sankhya darshavite aanee anek karkarog prakaranmadhye (udaa.jee. stun, swadupind, andashay, prostate). hii swakshari dii. aine. aii. double-strand break durustichya kamataratemule (kinwa samaroop punarsanyojan kamatarata) hote. signature 3 haah breakpointver microhomologies indelchya uchch bharashi sambandhit aahe.
apobeck enzymes.
cytidine deaminase enzymesche apobeck 3 kutumb vishanujanya genome sampadit karoon vishanujanya sansarganna pratisad dete, parantu "apobeck 3 aii" aanee "apobeck 3 bii" chya utsechak kriyakalapanmule avanchhit yazman genome sampadan hote aanee manvi papillomavirus-sambandhit karkaroganmadhye oncogenesismadhye dekhil sahbhagi houu shakate.
signature 2 aanee signature 13 heey see> tii aanee see> jee badalansathi samruddha aahet aanee heey edd/apobeck enzymes kutumbachya cytidine deaminase kriyakalapatun udbhavtat asey manale jaate.
apobeck3aii" aanee "apobeck3bii" yancha samavesh asalela germline vilopan bahurupata haah signature 2 aanee signature 13 utparivartananchya uchch bharanshi sambandhit aahe. stanachya karkarogachya jokhamisathi haah bahurupata madhyam pravesh (parshvabhoomichya jokhamipeksha duppat) manla jaato. apobeck-madhyasthi genome sampadanatil achook bhoomika aanee yantrana adyap purnapane chitrit keleli nahee, parantu sakriyakaran-prerit cytidine deaminase (madat)/apobeck complexes vishanujanya sansarg aanee lipid chayapachayas yazman rogpratikarak pratisadat sameel asalyache manale jaate.
cytidine deaminessesmule cytosine teey uracil badalane heey donhi signature 2 aanee signature 13 madhye vaishishtyapurn aahe. signature 2 madhye see [tii> see] aine badalyanche praman jaast aahe aanee signature 13 heey tii [see> jee] aine badalyanche praman jaast aahe. "apobeck3aii" aanee "apobeck3bii"-madhyasth utparivartanat pradhanyane pratikrutichya darmyan mage padnara dii. aine. aii. strand samavisht asato.
durustichi visangati.
chaar vaishvik utparivartaniy swakshya dii. aine. aii. visangati durustichya kamatarateshi sambandhit aahet aanee sookshm upgrah asthiratesah gathinmadhye aadhalalya aaheth swakshya 6,15,20 aanee 26. karya "emm. ell. etch. 1", "emm. ess. etch. 2", "emm. ess. etch. 6" kinwa "pii. emm. ess. 2" janukanmule sadosh dii. aine. aii. visangati durusti hote.
dii. aine. aii. proofreeding.
signature 10 madhye transcriptional bayas aahe aanee tii. pii. see. pii. tii. sandarbhat see> aii paryay tasech tii. pii. tii. pii. tii. pii. sandarbhat tii> jee paryayansathi samruddha aahe. signature 10 haah dii. aine. aii. polymerase epsilonchya badalalelya karyashi sambandhit aahe, jyamule dii. aine. aii. proofreeding kriyakalap qamee hoto. germline aanee somatik pole (januk) exonucles domain utparivartan donhi signature 10 shhee sambandhit aahet.
bases katri durusti.
sankraman utparivartanansathi sharirik sanwardhan (jeeh see> teeh aii) bases exzition repair (bair) kamatarateshi sambandhit aahe aanee colorectal karkarogatil sadosh "muthih", dii. aine. aii. glycosylaseshy sambandhit aahe. thet dii. aine. aii. auxidation nukasanamule 8-oxoguenine tayar hote, jeey jarr naan durust kele gele tarr dii. aine. aii. pratikrutichya darmyan cytosinaivaji edeninecha samavesh hoil. mutih heey edenine glycosylase enzymeche sanketankan karate, jeey 8-oxoguaninpasoon mell naan ghatalele edenine tayar karateh edenine bases pairing, tyamule kharab jhalele 8-oxoguanin kadhanyasathi "oo. jee. jee. 1" (oxoguanin glycosylase) aanee "naddi 1" (nudics hydrolage 1, jyala "emm. tii. etch. 1", mutt homolog 1 mhanoonahi olakhale jaate) yancha samavesh asalelya dii. aine. aii. durusti yantrana saksham karate.
bahya genotoxinchya samparkat yene.
nivadalele bahya genotoxin/carcinogen aanee tyanche utparivartan-prerit dii. aine. aii. nuksan aanee durusti yantrana vishisht aanvik swakshyanshi jodalya gelya aahet.
immunoglobulin januk hypermutation.
dirghakalin lymphocytic leukemia aanee ghatak bii-seela lymphomamadhye signature 9 olakhale gele aahe aanee tii> jee sankraman ghatanansathi vaishishtya sanwardhan kele gele aahe. heey truti-pravan polymerase (polh januk)-sambandhit utparivartanamule hote asey manale jaate.
alikade, polymerase truti-pravan sanshleshan swaksharicha sambandh gair-ganiteey karkaroganshi jodala gela aahe (udaa.jee. tvachecha karkarog) aanee vaay. see. jee. rachana utparivartanamadhye yogdan denyasathi gruheet dharale gele hote aanee tii. see. dynucleotides vadhichya paryayanche anshatah spashtikaran deu shakate.
itihas.
1990 chya dashakat, yuu. ess. national cancer institutemadhil curtis harris aanee baltimoremadhil johns hopkins oncology centermadhil bert woggelstein yanni aakadevaricha aadhava ghetala, jyat asey disun aale qee vividh prakarchya karkarogache pii53 madhye utparivartananche swatache adviteey sanch hote, jeey tambakhuchya dhuratil rasayne kinwa suryapasoonchya atinil prakashasarkhya vegvegalya ghatakanmule jhaale asanyachi shakyata hotee. pudhchya pidhichya anukramachya aagamanane, michael stratonne vaiyaktik arbudanmadhil anuvanshik badalambaddalachya aaplya samajamadhye kranti ghadavun aananyachi tantradnyanachi kshamata pahili, jyamule velakam senger institutechya dii. aine. aii.-anukraman yantranchya prachand banka arbudatil dii. aine. aii. chey pratyek akshar vachanyasathi karyarat jhalya. 2009 paryant, stratton aanee tyachya chamoone karkarogachya pahilya sampoorn genome anukramanchi nirmiti kelee hotee. heey tapshilvar nakashe hote jyat done vaiyaktik karkaroganmadhye jhalele serve anuvanshik badal aanee utparivartan darshavile gele hote-tvachecha melanoma aanee fuffusachi gaath. melanoma aanee fuffusachya karkarogache genome heey shaktishali purave hote qee karkarogamadhye vishisht doshinche botanche thase eka pramukh karanasah disu shakatat. yaa gathimadhye ajunahi anek utparivartan hote, jyanche spashtikaran atinil prakash kinwa tambakhuche dhoomrapan karoon deta yet navhate. guntaguntichya, anek kinwa agadi purnapane adnyat utpatti asalelya karkarogansathi guptaher karya adhik klisht jhaale. eka udaharan mhanoon, ekhadya nyayvaidhyak shastradnyane khunachya thikani botanchya thipkyansathi dhoolfek kelyachi kalpana qaraa. nyayvaidhyak shastradnya kadachit tyala bhagyavan tharu shakel aanee khidakichya patalavar kinwa daravaril handlever ekhadya dnyat marekashi julananya paripoorn chhapancha sanch sapadel. tathapi, pidit aanee sambhavya sanshayitanpasun teey nishpap paksh aanee polis tapaskartyanparyant-serve prakarchya prushthbhaganvar ekmekanvar thevalelya lokanchya sampoorn shrenishi sambandhit botanchya thipkyancha eka apaprakar ughad honyachi shakyata tyanna jaast asate. heey karkarogachya jeenomsarkhech aahe, jithe anek utparivartaniy namune samanyatah ekmekanvar aachchhadit kele jaatat, jyamule deta samajanyajoga hott nahee. sudaivane, stratoncha phd vidyarthi, ludmill alekzandrov yane ganitiyadrushtya samasya sodavanyacha eka marg shodhun kadhala. alekzandrovne dakhavun dile qee arbudamadhye aadhalanaya vaiyaktik utparivartananmadhil utparivartaniy namune andh srot pruthakkaran navachya ganiteey drushtikonacha vapar karoon ekmekanpasun vegale kele jaau shakatat. utparivartananchya navyane vighatit jhalelya namunyanna utparivartaniy swakshya asey mhatale gele. 2013 madhye, alekzandrov aanee stratton yanni karkarogachya genomics detamadhun utparivartaniy swakshya samajoon ghenyasathi pahili sanganakeey chaukat prakashit kelee. tyanantar, tyanni hii chaukat saat hajaranhun adhik karkarogachya janukanmadhye lagoo kelee aanee manvi karkarogatil utparivartaniy swakshyancha pahila sarvasamaveshak nakasha tayar keela. sadhya, manvi karkarogachya sampoorn sangrahamadhye shambharpeksha jaast utparivartaniy swakshya olakhalya gelya aahet. april 2022 madhye 58 naveen utparivartaniy swakshya varnan karnyat aalya.