Differential VHL Mutation Patterns nyob rau hauv Ob Sab Nthuav Cell RCC Distinguishes ntawm Kev ywj pheej Primary hlav thiab Contralateral Metastatic Kab Mob
May 24, 2023
Lub hom phiaj
Txhawm rau soj ntsuam seb puas yog ob sab, cov neeg mob multifocal clear cell carcinoma (ccRCC) tuaj yeem sib txawv los ntawm VHL kev hloov pauv mus rau hauv cov xwm txheej uas sawv cev rau ntau yam ntawm nws tus kheej tshwm sim thawj cov qog los yog ib lub qog loj uas tau kis ipsilaterally nrog rau lub raum contralateral. Qhov xwm txheej ntawm lub raum mob qog noj ntshav ntau yam sab nraud ntawm cov kab mob uas paub txog keeb kwm keeb kwm tseem tsis tau nkag siab.
Cov ntaub ntawv thiab cov txheej txheem
DNA los ntawm ntau cov qog nqaij hlav rau ib tus neeg mob tau soj ntsuam rau somatic VHL noob hloov thiab hypermethylation. Ib pawg ntawm cov qog nrog kev sib koom VHL kev hloov pauv tau txheeb xyuas nrog cov phiaj xwm, kev soj ntsuam tom ntej.
Cov txiaj ntsig
Cov pab pawg no muaj 5 cov neeg mob uas muaj ntau yam qog nqaij hlav uas pom tau tias muaj kev sib koom ua ke ntawm VHL kev hloov pauv raws li kev sib kis ntawm metastatic suav nrog rau lub raum contralateral. Hauv ntau qhov xwm txheej, qhov no tau lees paub los ntawm kev sib koom ua ke ntawm kev hloov pauv hauv ccRCC-txuas nrog cov noob. Nyob rau hauv sib piv, cov 14 cov neeg mob uas muaj ntau yam qog nqaij hlav pom txawv, unshared VHL alterations nyob rau hauv txhua txhua cov qog soj ntsuam, raws li nws tus kheej tshwm sim raum qog. Tsis muaj leej twg ntawm cov neeg mob tom kawg no tau pom muaj pov thawj ntawm kev sib kis hauv zos lossis nyob deb ntawm metastasis.
Xaus
Lub spectrum ntawm VHL hloov nyob rau hauv kev ntsuam xyuas ob sab, multifocal ccRCC hlav los ntawm ib tug neeg mob yuav paub qhov txawv ntawm ntau yam ywj siab qog loj hlob thiab metastasis. Qhov no tuaj yeem ua tau los ntawm kev tshuaj ntsuam genetic tests tam sim no thiab yuav txhim kho qhov tseeb ntawm tus neeg mob kev kuaj mob thiab kev kwv yees, nrog rau kev qhia txog kev tswj kom tsim nyog.
Nyem qhov no kom tau txaiscov txiaj ntsig ntawm Cistanche
Taw qhia
Clear cell renal cell carcinoma (ccRCC) yog hom mob qog noj ntshav ntau tshaj plaws, suav txog 75 feem pua ntawm cov neeg mob. Qhov kev kwv yees thiab kev tswj hwm ntawm cov neeg mob ccRCC yog nyob ntawm qhov chaw kho mob. Yog tias kuaj pom tus kab mob ntxov, thiab tseem nyob hauv thaj chaw hauv lub raum, kev phais kev phais yog cuam tshuam nrog 95 feem pua 5-10- xyoo muaj sia nyob. Txawm li cas los xij, yog tias cov qog tau kis hauv zos lossis hauv lub cev, 5- xyoo kev ciaj sia poob mus rau 67 feem pua lossis 12 feem pua. Clear cell RCC feem ntau tshwm sim los ntawm biallelic poob ntawm von-Hippel Lindau qog suppressor noob, VHL. Mechanistically, qhov no yog ua tiav los ntawm kev poob ntawm ib daim qauv ntawm chromosome 3p, suav nrog thaj av encoding VHL, ua ke nrog kev hloov pauv lossis txhawb nqa hypermethylation ntawm lwm daim ntawv ntawm VHL. Somatic VHL cov noob hloov pauv tau pom nyob rau hauv kwv yees li 90 feem pua ntawm cov ccRCC tsis sib xws, nrog cov noob hloov pauv pom nyob rau hauv ntau dua 80 feem pua ntawm ccRCCs thiab CpG kob txhawb nqa hypermethylation pom hauv kwv yees li 8 feem pua ntawm ccRCCs.
Thaum nyob rau hauv feem ntau ntawm cov kab mob ccRCC, tsuas muaj ib qho mob hauv ib lub raum xwb, feem ntau tshwm sim nrog ntau qhov mob hauv ib lossis ob lub raum. Cov neeg mob no nthuav tawm ob tog multifocal (BMF) ccRCC thiab qhov xwm txheej ntawm cov qog nqaij hlav no tuaj yeem cuam tshuam rau kev kuaj mob thiab kev tswj xyuas tus neeg mob. Qhov kev nthuav qhia tuaj yeem sawv cev rau tib lub qog qog uas tau kis nyob rau hauv lub raum ipsilateral lossis uas tau metastasized rau lub raum contralateral. Ntau qhov kev tshawb fawb tau tshawb xyuas cov xwm txheej ntawm multifocal ccRCC los ntawm kev sib piv ntawm qib ntawm 3p poob lossis qhov spectrum ntawm chromosomal alterations ntawm cov qog nyob rau hauv tib tus neeg mob los qhia tias lawv sib koom ib qho clonal keeb kwm zoo ib yam nrog metastatic kis los yog tias txhua tus qog sawv cev ntawm nws tus kheej tshwm sim. . Qhov kev puas tsuaj no tuaj yeem raug ntxias los ntawm ib puag ncig, xws li raug rau trichlorethylene (TCE), los yog vim muaj kev hloov pauv ntawm cov noob caj noob ces. Ib qho kev paub txog kev mob qog noj ntshav ob sab hauv ntau lub raum yog kev hloov pauv ntawm cov kab mob ntawm cov kab mob RCC, xws li VHL, MET, BAP1, lossis FLCN, cuam tshuam nrog cov qog nqaij hlav qog nqaij hlav. Feem ntau ntawm cov no yog kab mob von Hippel-Lindau (VHL), tshwm sim los ntawm cov kab mob hloov pauv ntawm VHL cov noob, uas ua rau muaj kev cuam tshuam rau ob sab multifocal ccRCC. Txawm hais tias qee tus neeg mob BMF ccRCC yuav muaj VHL syndrome, ntau tus neeg mob uas muaj kab mob sib txawv ntau yam yuav tsis kuaj pom RCC susceptibility syndrome.
Kev ntsuas qhov sib txawv ntawm cov kab mob metastatic lossis tus kab mob tshwm sim ntawm nws tus kheej tuaj yeem ua tau los ntawm kev tshuaj ntsuam genetic tsom xam ntawm cov qog los txheeb xyuas cov kev hloov pauv caj ces sib txawv, nyob rau hauv cov ntaub ntawv ntawm metastasis, lossis sib txawv ntawm cov kev hloov caj ces sib txawv hauv cov xwm txheej ywj pheej. Qhov sib txawv ntawm 2 qhov kev nthuav qhia kho mob no yog qhov tseem ceeb rau kev tswj hwm tus neeg mob. Yog tias metastasis tau tshwm sim, tus neeg mob feem ntau yuav raug kho rau cov kab mob hauv lub cev. Piv txwv li, yog tias tag nrho cov qog nqaij hlav muaj ntau yam kev ywj pheej nyob rau hauv lub raum, tus neeg mob yuav zoo li yuav raug kho rau cov kab mob hauv zos thiab raug tshawb xyuas cov kab mob genetic disorders nrog kev tshuaj ntsuam xyuas ntawm cov neeg hauv tsev neeg uas muaj feem yuav raug txiav txim siab.
Hauv txoj kev tshawb no, peb tau siv VHL noob hloov pauv hauv ccRCC los ua cov cim caj ces los sib piv cov qog hauv txhua tus neeg mob hauv ib pawg ntawm ob tog multifocal ccRCC cov neeg mob uas tsis paub txog kev hloov pauv caj ces. Ob tus neeg mob tau txheeb xyuas: cov neeg uas muaj cov qog nqaij hlav ntawm nws tus kheej thiab cov neeg uas muaj metastasis mus rau lub raum contralateral.
Cov teebmeem Cistanche
Cov ntaub ntawv thiab cov txheej txheem
1. Cov neeg mob
Cov neeg mob tau pom ntawm Urologic Oncology ceg (UOB) ntawm National Cancer Institute (NCI), National Institutes of Health (NIH) rau kev soj ntsuam kev soj ntsuam. Cov neeg mob tau raug suav hais tias muaj keeb kwm hauv tsev neeg yog tias lawv muaj tsawg kawg yog ib tus txheeb ze thib ib lossis thib ob uas muaj keeb kwm ntawm RCC ntshiab, thiab pib ntxov yog tias lawv tau kuaj pom thaum muaj hnub nyoog 46 lossis qis dua. Txoj kev tshawb no tau pom zoo los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Tshawb Fawb ntawm National Cancer Institute thiab txhua tus neeg mob tau sau ntawv tso cai pom zoo ntawm Urologic Oncology Branch raws tu qauv. Txhua tus neeg mob tau muab ib lub chaw kuaj mob uas tau txheeb xyuas 6- tus lej rau kev xa mus sab hauv.
2. PCR thiab DNA Sequencing
DNA tau muab rho tawm los ntawm cov ntshav thiab qog cov ntaub so ntswg siv Promega Maxwell 16 Ntshav thiab cov ntaub so ntswg DNA Purification Kits (Promega, WI,). DNA sequencing tau ua los ntawm PCR siv Qiagen Taq PCR Core Cov Khoom Siv (Qiagen, MD) raws li cov chaw tsim khoom tshwj xeeb, ua raws li kev sib txuas ua ke siv Big Dye Terminator v.1.1 Cycle Sequencing Kit (Applied Biosystems, CA) raws li cov chaw tsim khoom tshwj xeeb. thiab khiav ntawm ABI 3130xl lossis 3730 Genetic Analyzer (Applied Biosystems, CA). Sanger Sequencing tau ua nyob rau ntawm CCR Genomics Core ntawm National Cancer Institute, NIH, Bethesda, MD 20892. Forward thiab reverse sequences raug soj ntsuam siv Sequencher 5.0.1 (Genecodes, MI).
3. DNA Methylation Analysis
DNAs tau raug kho bisulfite siv Qiagen EpiTect Bisulfite Kit (Qiagen, MD) raws li cov chaw tsim khoom tshwj xeeb. Ob tug primer khub tau tsim uas yuav muaj peev xwm ntawm annealing rau ob qho tib si methylated thiab unmethylated/bisulfite-hloov DNA nyob rau hauv ib ncig ntawm lub VHL txhawb nqa. PCR tau ua raws li saum toj no nrog cov txheej txheem sab nrauv, ua raws li qhov thib ob ntawm PCR nrog cov primers sab hauv, thiab cov khoom tau raug muab faib ua ob ntu raws li saum toj no.
4. Oncomine thiab TruSight Oncology 500 Kev Ntsuam Xyuas
Xaiv cov qog los ntawm cov kws kho mob qhia txog kev phais raug xaiv rau kev tshuaj xyuas los ntawm Oncomine Comprehensive Assay v3 (ThermoFisher, MA) lossis tom qab ntawd, TruSight Oncology 500 (Illumina, CA), tiam tom ntej sequencing assays muaj peev xwm kuaj pom ib qho nucleotide variations, luam tus lej variations. gene fusions thiab indels los ntawm 161 mus rau 523 tus neeg tsav tsheb qog noj ntshav, feem. Formalin-taw, paraffin-embedded kuaj tau ua tiav los ntawm Molecular Diagnostics Section ntawm Laboratory of Pathology ntawm NCI.
Standardized Cistanche
Kev sib tham
Kev muaj peev xwm ua tau zoo dua rau cov neeg mob uas muaj ob sab ntau lub raum qog yuav ua rau muaj kev tswj hwm tus neeg mob zoo dua thiab tuaj yeem ua rau muaj kev nkag siab tshiab rau hauv cov caj ces ntawm lub raum cell carcinoma. Feem ntau, tsis tshua muaj kev paub txog kev hloov pauv ntawm ob sab multifocal ccRCC. Qhov zaus ntawm ob sab thiab/los yog multifocal RCC nyob rau hauv kev nthuav qhia los yog nyob rau hauv ib lub xyoo ntawm kev tshawb pom qog nqaij hlav yog qhov tsawg thiab cov zaus tshaj tawm nws txawv heev ntawm 0.8 feem pua rau 5.4 feem pua. Cov kev tshawb fawb ntxiv ntawm cov pab pawg loj dua nrog cov txheej txheem kuaj mob thoob ntiaj teb yuav tsum ua kom paub tseeb qhov tseeb ntawm BMF ccRCC. Wiklund et al tau tshaj tawm tias BMF RCC feem ntau tshwm sim hauv cov neeg mob hluas thiab Syed li al tau pom tias muaj kev pheej hmoo ntau ntxiv nrog kev rov qab mus ntev dua. Ob peb txoj kev tshawb fawb tau tshawb xyuas seb puas yog multifocal RCC sawv cev rau hauv zos metastasis lossis nws tus kheej tshwm sim los ntawm kev sib piv ntawm qib ntawm 3p poob los yog spectrum ntawm chromosomal alterations ntawm cov qog nyob rau hauv tib tus neeg mob. Miyake et al thiab Junker et al ob leeg tau pom cov qauv sib koom ntawm chromosome 3p poob lossis chromosomal hloov pauv ntawm cov qog hauv tib tus neeg mob raws li kev sib kis ntawm metastatic, thaum Ji thiab al pom txawv qib ntawm 3p poob ntawm cov qog los ntawm 2 tus neeg mob sib txawv raws li nws tus kheej tshwm sim. qog nqaij hlav hauv ob qho tib si. Ob peb cov ntaub ntawv qhia pom cov pov thawj ntawm metastatic kis los ntawm 1 lub raum mus rau lub raum contralateral, adrenal, los yog raum cheeb tsam.
Hauv kev tshawb fawb tam sim no, txhua tus neeg mob tau tsim cov qog hauv ob lub raum. Tus kab mob metachronous muaj ntau dua (4/5; 80 feem pua) nyob rau hauv cov pab pawg uas pom contralateral metastases dua li cov qog hlav loj hlob ntawm nws tus kheej (3/14; 21 feem pua), tab sis ob qho tib si synchronous thiab metachronous contralateral kab mob tau pom nyob rau hauv ob qho tib si cohorts. . Kev soj ntsuam ntawm tus qauv ntawm VHL kev hloov pauv ntawm cov qog los ntawm txhua tus neeg mob tau tso cai rau txhua tus neeg mob raug xaiv los ntawm kev txhawj xeeb txog tus kab mob metastatic lossis cov qog hauv ob sab hauv lub raum yuav tshwm sim ntawm nws tus kheej. Cov neeg mob uas muaj tus kab mob metastatic tau sib koom ib qho kev hloov pauv ntawm VHL ntawm tag nrho cov qog, thaum cov neeg mob uas nws tus kheej tshwm sim raum qog muaj qhov sib txawv VHL hloov hauv cov qog sib txawv.
Cov neeg mob uas pom tau tias muaj kev sib koom ua ke VHL hloov pauv hauv ntau lub raum qog tuaj yeem tshwm sim los ntawm cov kab mob mosaicism VHL hloov pauv ntau dua li metastasis. Nyob rau hauv cov ntaub ntawv no, cov germline hloov pauv tsuas yog nyob rau hauv lub raum hlwb, los yog txawm ib feem ntawm lub raum hlwb, tab sis tsis muaj nyob rau hauv cov qe ntshav dawb ntsuas nyob rau hauv ib tug kuaj ntshav los yog lub buccal hlwb los ntawm lub puab tsaig swab. Tus neeg mob yuav pom cov kab mob tsis zoo los ntawm kev ntsuas tus qauv tab sis tuaj yeem muaj qhov hloov pauv VHL tib yam tam sim no nyob rau hauv ntau cov qog nqaij hlav ntawm nws tus kheej. Lub hauv paus ntsiab lus no tsis ntev los no tau pom nyob rau hauv Wilms cov neeg mob qog nqaij hlav uas muaj kev hloov pauv thaum ntxov ntawm txoj kev loj hlob uas ua rau cov qog nqaij hlav ntawm ob sab nrog rau kev sib koom tsav tsheb. Qhov tseem ceeb, nws kuj tau pom tias nyob rau hauv qhov xwm txheej no cov qog nqaij hlav ywj pheej yuav tsim cov kev hloov pauv tshwj xeeb ntxiv raws li cov qog hloov zuj zus. Feem ntau, mosaicism yog qhov tsis tshua muaj tshwm sim thiab tsis zoo li hauv txoj kev tshawb no vim tias 3 tus neeg mob tau pom cov qog nrog sib koom ntxiv kev hloov pauv ntawm cov noob caj noob ces (MTOR thiab AID1A rau Tus Neeg Mob 3; PBRM1, SETD2, thiab NFE2L2 rau Tus Neeg Mob 4; PBRM1 thiab KDM5C rau Tus Neeg Mob 5) uas tuaj yeem tsuas yog sib koom vim metastasis es tsis yog mosaicism. Tsis tas li ntawd, 2 cov neeg mob uas muaj kev sib koom VHL kev hloov pauv (Cov neeg mob 2 thiab 3) kuj tau ua tiav ntawm cov ntaub so ntswg hauv lub raum uas tsis muaj pov thawj ntawm VHL kev hloov pauv. Thaum kawg, 4 ntawm 5 tus neeg mob (Cov neeg mob 1 txog 4) tau tsim metastases sab nraum lub raum
Nco ntsoov, tus neeg mob 5 tseem tsis tau pom cov pov thawj ntawm cov metastases nyob deb. Thaum nws cov qog loj tshaj plaws yog 4.8 cm thiab nws tuaj yeem suav hais tias muaj kev pheej hmoo siab dua rau kev kis tus kabmob metastatic, qhov kev soj ntsuam tias tag nrho 7 ntawm nws cov qog nqaij hlav tsis ntev los no qhia txog kev hloov pauv ntawm VHL thiab feem ntau sib koom PBRM1 thiab KDM5C kev hloov pauv ua rau muaj kev cia siab rau cov metastases nyob deb dua. Yog li ntawd, tus neeg mob no yuav tau ua raws li kev ceev faj tshwj xeeb thiab kev soj ntsuam ze rau yav tom ntej.
Cistanche tshuaj thiab qhuav Cistanche
Cov neeg mob uas nws tus kheej tshwm sim raum qog pom tau tias muaj txiaj ntsig zoo rau ob tsev neeg keeb kwm ntawm mob qog noj ntshav raum thiab kab mob thaum ntxov, ob qho tib si yog qhov qhia txog kev hloov pauv ntawm cov noob qoob loo. Txhua tus neeg mob tau kuaj pom qhov tsis zoo rau lub raum mob qog noj ntshav gene pathogenic variations, qhia tias lwm yam tsis paub txog caj ces tuaj yeem tshwm sim. Germline translocation cuam tshuam nrog chromosome 3p kuj tau pom tias yuav ua rau muaj kev pheej hmoo ntawm ccRCC thiab muaj feem cuam tshuam nrog ob sab ntau yam kab mob. Kev hloov pauv tsis tuaj yeem tshawb pom los ntawm cov phiaj xwm gene arrays thiab xav tau kev tshuaj xyuas karyotype. Yog li, cov neeg mob uas nws tus kheej tshwm sim rau lub raum qog uas tam sim no tsis muaj kev hloov pauv hauv RCC paub cov noob caj noob ces yuav tsum tau kuaj xyuas chromosome 3p translocations. Kev tshuaj xyuas Karyotype muaj rau 12 ntawm 14 ntawm cov neeg mob uas muaj cov qog nqaij hlav hauv lub raum ntawm nws tus kheej hauv txoj kev tshawb no, tab sis tsis muaj qhov cuam tshuam txog kev hloov pauv. Kev ntsuam xyuas ntxiv ntawm cov neeg mob no rau kev hloov pauv ntawm cov kab mob ntxiv tuaj yeem txheeb xyuas cov kab mob RCC tshiab thiab cov VHL hloov spectrum tsom xam tso cai rau kev xaiv cov neeg mob no.
Nws tau dhau los ua ntau zuj zus los ua qhov kev tsom xam cov qog nqaij hlav qog nqaij hlav ntawm cov neeg mob qog lossis biopsies, thiab cov kev tshuaj ntsuam no feem ntau suav nrog VHL cov noob thiab ntxiv ccRCC cov noob caj noob ces xws li PBRM1, BAP1, SETD2, thiab ARID1A. Yog li ntawd, niaj hnub bilateral biopsies ntawm ob sab ob lub raum masses yuav muab ib tug yooj yim thiab npaum txoj kev rau kev paub qhov txawv ntawm contralateral metastasis thiab nws tus kheej tshwm sim multifocal hlav, as opposed to the chromosomal alteration-based analysis that have been educated, tso cai rau kev paub ntxiv hauv cov neeg mob. kab mob metastatic. Ntau qhov kev tshawb fawb tsis ntev los no tau hais txog qhov sib txawv ntawm intratumoral heterogeneity tam sim no nyob rau hauv ccRCC thiab qhov no tuaj yeem cuam tshuam kev tshuaj ntsuam xyuas biopsy raws li thaj chaw kuaj pom yuav tsis muaj kev hloov pauv uas tsuas muaj nyob rau qee thaj chaw ntawm cov qog thiab muab cov txiaj ntsig tsis raug. Qhov zoo ntawm kev ntsuam xyuas VHL kev hloov pauv yog tias nws muaj nyob rau hauv feem ntau ccRCCs thiab yog qhov kev hloov pauv ntawm lub cev thaum ntxov uas yuav muaj nyob thoob plaws hauv cov qog nqaij hlav, yog li biopsies yuav luag ib txwm muaj kev qhia.
Qhov tseem ceeb ntawm kev muaj peev xwm paub qhov txawv ntawm cov neeg mob uas muaj kab mob metastatic los yog hauv zos ntawm nws tus kheej tshwm sim cov qog nqaij hlav hauv lub raum yog tias lawv yuav raug tswj hwm qhov sib txawv thiab muaj peev xwm muaj txiaj ntsig sib txawv. Thaum cov pov thawj ntawm metastasis sab nraud ntawm lub raum yog qhov tseeb, cov duab ntawm cov neeg mob uas muaj BMF ccRCC tsis tso cai rau qhov raug xaiv. Hauv txoj kev tshawb no, qhov teeb meem no yog qhov piv txwv zoo tshaj plaws los ntawm Cov Neeg Mob 4, 9, thiab 19 raws li tag nrho 3 tau nthuav tawm nrog cov kab mob ob sab nrog cov qog loj hauv ib lub raum thiab cov qog me me lossis cov qog nqaij hlav hauv lub raum contralateral thiab tsis muaj pov thawj synchronous ntawm cov kab mob sab nraud. raum. Yog tsis muaj VHL kev hloov pauv, qhov pom tsuas yog qhov pom tau tias Tus Neeg Mob 19 muaj qhov pib yau tshaj plaws thaum muaj hnub nyoog 36, thiab Tus Neeg Mob 9 tau pib qhov tseeb thaum muaj hnub nyoog 62. Kev ntsuam xyuas ntawm VHL kev hloov pauv tau pom tias ob tus neeg mob 9 thiab 19 muaj qhov sib txawv ntawm VHL hauv cov qog sib txawv, raws li nws tus kheej tshwm sim raum qog. Hloov pauv, Tus Neeg Mob 3 muaj qhov sib koom VHL kev hloov pauv hauv txhua cov qog ua raws li cov hauv paus chiv keeb thiab contralateral metastasis. Qhov no tau txais kev txhawb nqa los ntawm kev sib koom ua ke ntawm kev sib koom ntxiv somatic hloov pauv hauv MTOR thiab ARID1A hauv txhua tus neeg mob 3 cov qog. Yog li, Cov Neeg Mob 9 thiab 19 tuaj yeem kho tau los ntawm kev phais tshem tawm ntawm cov qog thiab kev soj ntsuam niaj hnub, thaum Tus Neeg Mob 3 yuav raug kho nrog cov kev kho mob tsim nyog rau tus neeg mob uas muaj kab mob metastatic.
Hauv kev xaus, kev soj ntsuam ntawm kev hloov pauv ntawm VHL hauv BMF ccRCC tuaj yeem pab kom paub qhov txawv ntawm qhov sib txawv ntawm cov qog nqaij hlav hauv lub raum thiab hauv zos, nws tus kheej tshwm sim raum qog thiab qhov no tuaj yeem siv los cuam tshuam cov neeg mob kev tswj hwm thiab cov txiaj ntsig.
Cov ntaub ntawv
1. Linehan WM, Walther MM, Zbar B. Lub hauv paus caj ces ntawm mob qog noj ntshav ntawm lub raum. J Urol. 2003; 170(6 Pt 1): 2163–2172.
2. Chin AI, Lam JS, Figlin RA, Belldegrun AS. Kev soj ntsuam cov tswv yim rau cov neeg mob lub raum cell carcinoma tom qab nephrectomy. Rev Urol. 2006; 8:1–7.
3. Shao N, Wan F, Abudurexiti M, Wang J, Zhu Y, Ye D. Ua rau muaj kev tuag thiab kev muaj sia nyob ntawm lub raum cell carcinoma. Pem hauv ntej Oncol. Xyoo 2019; 9:591.
4. Gnarra JR, Tory K, Weng Y, et al. Kev hloov pauv ntawm VHL qog suppressor gene hauv lub raum carcinoma. Nat Genet. 1994; 7:85–90.
5. Nickerson ML, Jaeger E, Shi Y, et al. Txhim kho kev txheeb xyuas ntawm von Hippel-Lindau gene hloov pauv hauv cov qog nqaij hlav hauv lub raum. Clin Cancer Res. 2008; 14:4726–4734.
6. Cancer genome atlas research n. Kev nthuav dav molecular characterization ntawm ntshiab cell raum cell carcinoma. Xwm. 2013; 499:43–49.
7. Zbar B, Brauch H, Talmadge C, Linehan M. Poob alleles ntawm loci ntawm caj npab luv ntawm chromosome 3 nyob rau hauv lub raum cell carcinoma. Xwm. 1987; 327: 721–724.
8. Ricketts CJ, Linehan WM. Multi-regional sequencing elucidates evolution ntawm ntshiab cell cell carcinoma. Cell. 2018; 173:540–542.
9. Syed JS, Nguyen KA, Holford TR, Hofmann JN, Shuch B. Risk factor for metachronous bilateral renal cell carcinoma: Kev soj ntsuam, kab mob sib kis, thiab kev soj ntsuam cov txiaj ntsig. Mob qog noj ntshav. 2019; 125:232–238.
10. Crispen PL, Lohse CM, Blute ML. Multifocal renal cell carcinoma: clinicopathologic nta thiab tshwm sim rau cov qog
11. Wiklund F, Tretli S, Choueiri TK, Signoretti S, Fall K, HO Adami. Risk ntawm ob sab raum mob qog noj ntshav. J Clin Oncol. 2009; 27:3737–3741.
12. Ji Z, Zhao J, Zhao T, Han Y, Zhang Y, Ye H. Independent qog keeb hauv ob kis ntawm synchronous bilateral clear cell carcinoma. Sci Rep. 2016; 6:29267.
13. Miyake H, Nakamura H, Hara I, et al. Multifocal renal cell carcinoma: pov thawj rau ib hom clonal keeb kwm. Clin Cancer Res. 1998; 4:2491–2494.
14. Junker K, Thrum K, Schlichter A, Muller G, Hindermann W, Schubert J. Clonal keeb kwm ntawm multifocal renal cell carcinoma raws li txiav txim los ntawm microsatellite tsom xam. Phau ntawv Journal of Urology. 2002; 168:2632–2636.
15. Wells GM, Schroth W, Brauch H, Ross EA. Ob sab lub raum-cell carcinoma cuam tshuam nrog kev hloov pauv ntawm VHL thiab kev raug trichlorethylene mus ntev. Clin Nephrol. 2009; 71:708–713.
16. Linehan WM. Lub hauv paus caj ces ntawm ob lub raum mob qog noj ntshav: cuam tshuam rau kev ntsuam xyuas thiab kev tswj hwm. J Clin Oncol. 2009; 27:3731–3733.
17. Linehan WM, Srinivasan R, Schmidt LS. Lub hauv paus caj ces ntawm lub raum mob cancer: kab mob metabolic. Nat Rev Urol. 2010; 7:277–285.
18. Linehan WM, Ricketts CJ. Lub hauv paus metabolic ntawm lub raum mob cancer. Semin Cancer Bio. 2013; 23:46–55.
19. Latif F, Tory K, Gnarra J, et al. Kev txheeb xyuas ntawm tus kab mob von Hippel-Lindau mob qog suppressor gene. Kev tshawb fawb. 1993; 260:1317–1320.
20. Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau kab mob: genetic, Clinical, and imaging features. Xov tooj cua. 1995; 194:629–642.
21. Kechrid M, Malik GH, Al-Mohaya S, et al. Lub raum cell carcinoma ntawm contralateral ob lub raum nrog cov thib ob hauv lub gallbladder yim xyoo tom qab nephrectomy. Saudi J Raum Dis Transpl. 2000; 11:587–592.
22. Wang K, Wang J, Sun JI, et al. Lub raum cell carcinoma nrog metachronous metastasis mus rau contralateral adrenal qog thiab zis zais zis: Cov ntaub ntawv qhia. Oncol Lett. 2015; 10:2749–2752.
23. Ahmed HK, Bapir R, Abdula GF, Hassan KMS, Ali RM, Salih MA. Ib leeg contralateral adrenal metastasis ntawm lub raum cell carcinoma 15 xyoo tom qab radical nephrectomy: Cov ntaub ntawv qhia thiab tshuaj xyuas cov ntaub ntawv. Int J Surg Case Rep. 2019; 58:33–36.
24. Coorens THH, Treger TD, Al-Saadi R, et al. Embryonal precursors ntawm Wilms qog. Kev tshawb fawb. 2019; 366: 1247–1251.
25. Foulkes WD, Polak P. Ob leeg qog nqaij hlav - Tau txais lossis tau txais? N Engl J Med. 2020; 383:280–282.
26. Cohen AJ, Li FP, Berg S, et al. Hereditary renal-cell carcinoma txuam nrog chromosomal translocation. N Engl J Med. 1979; 301: 592–595.
27. Foster RE, Abdulrahman M, Morris MR, et al. Tus cwj pwm ntawm 3; 6 translocation txuam nrog raum cell carcinoma. Genes Chromosomes Cancer. 2007; 46:311–317.
28. Gerlinger M, Horswell S, Larkin J, et al. Genomic architecture thiab evolution ntawm ntshiab cell cell carcinomas txhais los ntawm multiregion sequencing. Nat Genet. 2014; 46:225–233.
29. Turajlic S, Xu H, Litchfield K, et al. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. Cell. 2018; 173:595–610. e511 ua.
Cathy D. Vocke, Christopher J. Ricketts, Adam R. Metwalli, Peter A. Pinto, Rabinndra Gautam, Mark Raffeld, Maria J. Merino, Mark W. Ball, thiab W. Marston Linehan
