Li-Fraumeni syndrome, kana kuti LFS, iine chimiro chemagariro chinokonzera vanhu kune marudzi akasiyana-siyana emukenza. Vanhu vane LFS vanowanzotanga ma kancita pakutanga kwehupenyu kupfuura izvo zvinowanzoonekwa nevanhu vakawanda. Ikoko kunogonawo kuva nemukana mukuru wemakondomu echipiri kana anotevera muLFS.
Chirwere chacho chakatanga kuzivikanwa mumhuri dzinoverengeka dzakagadzira zvirwere zvakasiyana-siyana zvekenza, kunyanya sarcomas, pakutanga kwehupenyu.
Uyezve, nhengo dzemhuri dzakaonekwa kuti dzinowanzoita kuti dzive nekenza dzakawanda, itsva uye dzakasiyana-siyana pamusoro pehupenyu hwose. Frederick Li naJoseph Fraumeni, Jr, vakanga vari vanachiremba vakatanga kutaurira pamusoro pezviwanikwa izvi muna 1969, uye ndizvo zvakaita kuti LFS iwane zita racho.
Nei Kune Ngozi Yakanyanya Yekenza?
Vanhu vane Li-Fraumeni syndrome vane njodzi yakanyanya yekenza nokuti vakagara nhaka yezvinozivikanwa segermine mutation mune rimwe geni rinokosha rinonzi TP53.
Mushonga wokuchinja mutsva ndiko kuchinja kwechimiro chakange chakaitika mujecha revabereki vevamwe vakavhiringidzika-kureva kuti, kuchinja kunotanga kuitika mumasero ari mavha mavari kana ma testes anopa mazai nehuta. Kuchinja kwemukati mumasero aya ndiyo chete mhando dzeshanduko dzinogona kupfuudzwa zvakananga kuvana panguva yekubata apo zamu nehuta zvinosangana kuti zvive zygote. Nokudaro, germine mutations inochinja masero ose mumuviri wevana vatsva; Kusiyana neizvi, somatic mutations inokura pane imwe nzvimbo pane imwe nguva mushure mekuberekwa, kana zvakawanda, zvizhinji gare gare, uye zvinokanganisa nhamba yakasiyana yemasero mumuviri.
Iko kunotenderera kwemajeri mumhuri dzine LFS ndiyo iyo inobata basa rejeni re TP53. Munyika yekutsvakurudza kwekenza, mutero we TP53 wakanyanyisa zvikuru zvokuti wakanzi "mutariri we genome."
TP53 inorambidza zvinokonzera maronda-ndiko kuti, inhengo inodzivirira sero kubva pane imwe danho panzira yekuenda kune kenza.
Apo iyo jenisi inotenderera zvakadai zvokuti haigoni kushanda sezvinodiwa, kana kuti kuti basa rayo riwedzere kuderedzwa, sero rinogona kufambira mberi kune kenza, kazhinji iri pamwe chete nedzimwe mararamiro ekuchinja. Kuongororwa kwe TP53 germline mutations yakatanga kusimbiswa muna 1990 apo kubatana pakati p53 neLFS kwakasimbiswa. Kubvira panguva iyo, zvinenge makumi mapfumbamwe nemakumi mana nemakumi mashanu kubva mumutambo we TP53 zvakawanikwa.
Kuchinja mune imwe gene, hCHK2, kwave kuchibatanidzwa neLFS, zvisinei, kukosha kwayo hakusi pachena. IHCHK2 geni ndiyo inodzvinyirira chiremera chinoshandiswa mukugadzirisa DNA kukanganisa. Nhamba shomanana yemhuri inotakura mutambo uyu, uye avo vanobatwa vane mararamiro akafanana akadai seaya ane mutsauko we TP53.
Nengozi Ndeipi?
Izvo zvave zvichifungidzirwa kuti, zvakakwana, munhu ane LFS ane 50 muzana yekana yekuva nekenza nemakore makumi mana uye makumi mapfumbamwe kubva muzana mukana wezera remakore makumi matanhatu. Kana uine LFS, njodzi yako pachako inowanzoenderana pasinei iwe uri mukomana kana mukadzi, nevakadzi vanowanzova nehuwandu hwakanyanya kupfuura varume.
Kana iwe ukatarisa mungozi yehupenyu hwekenza mune varume nevakadzi vane LFS pazera remakore makumi mashanu, ipapo ngozi yekuve nekenza inoputsa sezvinotevera: 93 muzana yevakadzi uye 68 muzana yevarume.
Kana ivo vachiva nekenza, vakadzi vanoitawo kukura iyo kenza pamakore ekutanga: makore makumi maviri nemashanu, pamavhareji, zvichienderana nemakore makumi mana emakore muvarume.
Iyo ngozi yakakwirira yevakadzi inonyanya kukonzerwa nekenza yepamuviri-yekutanga yepamu, maererano nekudzidza naMai nevamwe. Vatsvakurudzi vakaonawo kuti, pakati pevakadzi vakaratidza zvakanaka kune mutsika ye TP53, kenza yemazamu ndiyo yaive yakawanda kwazvo yakaipa. Kuwedzera kwechirwere chepabonde kuwedzera kwaiva neavo 85 muzana nezera remakore makumi matanhatu. Padzidzo imwechete, ngozi yekenza yepamu yakawedzera zvikuru munguva yemakore makumi maviri emukadzi, ichiratidza kuti kuongorora kenza yepabonde kunotanga nemakore makumi maviri ndiyo tsika yakanaka kune vakadzi vane LFS.
Iyi yehutano yekutengesa kweTP53 yakafanana neyeiyo inowanikwa nevakadzi vane mishonga yegermine muBrCA1 neBrCA2-mazamu aya akasimudza mukurumbira nehuwandu hwemashoko pamusoro pekuberekwa kweBRECA1 / 2 uye mastectomies ekudzivirira (nevanozivikanwa sa Angelina Jolie).
Chii Chinonzi Cancers Core Chinobatanidzwa?
Cheropi kenza inogona kukura mumunhu chero ipi zvayo panguva ipi zvayo. Zvisinei, vanhu vane LFS vanozivikanwa kuva nekenza yenguva yekuongorora zvirwere uye ngozi yehupenyu hwemhando dzakawanda dze "core" marudzi ekenza, kusanganisira zvinotevera:
- Osteosarcoma -inonyanya kurudzi rwekenza inotanga mumapfupa
- Sarcomas dzakasvibirira -rudzi rwekenza inobva kune dzimwe mishonga, zvakadai semafuta, mutsvuku, mitsipa, mashupu, mishonga yeropa, kana midzi yakadzika yeganda
- Kenza yepabonde yekutanga
- Uturu hwebongo
- Leukemia -kenza yeropa-forming cells
- Adrenal cortical carcinoma -a kenza yeAdrenal cortex, iyo inowanikwa kunze kwezvinyorwa zvinonzi adrenal. Izvo zvinoratidzira zvinowanikwa pamusoro peitsvo uye inotora basa rinokosha mumabasa akasiyana-siyana ehomoni.
Mukudzidza kwakaitwa naKleihues muna 1997, inowanzozivikanwa sarcoma muLFS yaiva osteosarcoma, inowirirana ne12,6 muzana yezviitiko, yakateverwa nemakumbo emakumbo (12 muzana) uye sarcomas dzakapfava (11.6 muzana). Pakati pemasarumas anonyorova, rhabdomyosarcomas (RMS) ndiyo inowanzozivikanwa. Dzimwe sarcomas dzinowanzotaurwa dzinosanganisira fibrosarcomas (iyo isisati yaonekwa sechinhu chechokwadi), inypical fibroxanthomas, leiomyosarcomas, orbital liposarcomas, spindle cell sarcomas, uye sarcomas dzisina kufanira. Hematological neoplasms, kana zvirwere zveropa (zvakadai seacute lymphoblastic leukemia neHodgkin's lymphoma) uye adrenocortical carcinomas yakaitika panguva yakawanda ye 4.2 uye 3.6 muzana, zvichienderana.
Sezvo mhuri dzakawanda dzine ruzivo rwechimiro inofananidzwa neLFS dzave dzakaonekwa, dzakawanda zvirwere zvekenza zvakabatanidzwa.
Muchirwere wekenza weLFS wakawedzera kuti uve nemaranoma, mapapu, matumbo, utachiona, ovarian, uye mamwe makondombera.
Kubva pakuongorora kwetsika, pangozi yekuita sarcoma-soft-tishu uye kenza dzeuropi inoratidzika kuva yakakura muhuduku, asi njodzi yeasteosarcoma inogona kuva yakakwirira munguva yevechiri kuyaruka, uye ngozi yekenza yepamukadzi inowedzera zvikuru kusvika kune makore makumi maviri uye inoenderera mberi kuva yakwegura munhu mukuru. Iyi nhamba inoshandiswa kuchinja, zvisinei, sezvo miitiro yekuongororwa nekenza-yakagadzirirwa maitiro eve iri kuchinja.
Li-Fraumeni Syndrome Inotsanangurwa Sei?
Kune nzira dzakasiyana-siyana uye tsanangudzo dzechirwere ichi. Zvimwe zvinowanzobatanidzwa kune vamwe. Classic LFS ndiyo inonyanya kutsanangurwa, sezvo inoda sarcoma kugadziriswa vasati vava nemakore makumi mashanu, nepo tsanangudzo dzinotevera dzakadai seChitter criteria yakaedza kufambira mberi mune zivo yesayenzi pamusoro pemararamiro evanhu uye makore anotevera kuongororwa.
Zvirongwa zvekare zveLFS:
- Iwe unorwara uine sarcoma (rudzi rwechirwere runosanganisira masero emasumbu / maronda / majoints / mafuta anotangira) asati asvika makore makumi mashanu nemakore
- Chikoro chekutanga-mubereki (mubereki, mukoma kana mwana kana mwana) ane kenza ipi inowanikwa musati yave nemakore makumi mashanu nemashanu
- Chimwe chekutanga-kana yechipiri-chidimbu (inosanganisira vanun'una, vanamume, uyewo) nemupi wepabonde unowanikwa musati wava nemakore makumi mashanu kana kuti sarcoma inowanikwa pane imwe nguva.
Li-Fraumeni-like (LFL) zvinotarisirwa:
- Nzira yeLFL inokonzera mambure akawandisa kusanganisira mamwe mhando dzekenza uye inosanganisira dzimwe hama dzinowanikwa shure kwezera remakore makumi mashanu, uye kune tsanangudzo mbiri dzakasiyana mukushandiswa:
- Birch tsanangudzo: Iwe unorwara uye une kenza chero ipi zvayo yevana kana sarcoma, chirwere chepfungwa, kana kuti adrenocortical carcinoma inoratidzika musati wava nemakore makumi mashanu nemashanu uye yechipiri-yechipiri chechipiri nechirwere chekare cheLi-Fraumeni (sarcoma, kenza yemazamu, tumori yepfungwa, adrenocortical carcinoma, kana leukemia) chero ipi zvayo uye imwe yekutanga-kana yechipiri-yechipiri nemukenza chero upi zvake makore makumi matanhatu asati apfuura.
- Eels tsanangudzo: Une 2 yekutanga-kana yechipiri-degree hama neLi-Fraumeni-related malignancies (sarcoma, kenza yemazamu, tumori yeuropi, leukemia, tumorous adoreocortical, melanoma, kenza ye prostate, kenza yepancreatic) chero ipi zvayo.
Chompret criteria:
- Iwe une chiremera cheLi-Fraumeni tumor spectrum (soft-tissue sarcoma, osteosarcoma, kenza yepremenopausal breast, brain tumor, adrenocortical carcinoma, leukemia, kana chirwere chemaperembudzi chemapapu) asati asvika makore makumi mana nemakore ekutanga- dhigirii inosangana neEi-Fraumeni tumor (kunze kwekenza yemazamu, kana iwe une kenza yemazamu) usati wava nemakore makumi mashanu kana kuti ane tumorama yakawanda kana kuti
- Une maronda akawanda (kunze kwemafupa akawanda emvere), 2 ayo anowanikwa muEt-Fraumeni tumor spectrum uye yekutanga yakaitika isati yasvika makore 46 kana kuti
- Iwe unorwara uine adrenocortical carcinoma kana choroid plexus tumor, pasinei nemamiriro emhuri.
Maererano nekuongororwa kweLFS naSchneider uye vashandi pamwe navo, zvinenge makumi manomwe kubva muzana zvevanhu vakawana chirwere chechirwere (kureva, kushandura tsanangudzo dzakadai sepamusoro) vane chimiro chinokuvadza chinoshanduka mumhepo muTV53 chirwere chinopisa.
Kutarisira Kwekenza
Kana munhu ane LFS achikura nekenza, nguva dzose kenza inorambidzwa inokurudzirwa, kunze kwekenza yemazamu, iyo inonzi mastectomy, pane lumpectomy, inokurudzirwa kuitira kuti kuderedze njodzi dzekenza yechipiri yepamuviri uyewo kudzivisa kurapwa kwemaawa.
Vaya vane LFS vanorayirwa kuti vasave nehutachiona hwemazuva ose kana zvichibvira kuitira kuti kuderedza dambudziko rechidimbu chechidimbu-induced malignancies. Zvisinei, apo majekesa anoonekwa semishonga anodiwa kuti awedzere mukana wekupona kubva pane kupiwa kwakaitwa, inogona kushandiswa pakuziva kwechiremba uye kurapa.
Kuongorora uye Kuongororwa
Pakave nekukumbira kuongorori kune nyanzvi kugadzira kubvumirana nezvekuti mhuri dzine FLS dzinofanira kuongororwa uye kutarisirwa sei. Zvinosuruvarisa, nepo sayenzi ichikurumidza kukurumidza, hapana kubvumirana kwakadaro kuripo kune dzose.
Kuwedzerwa kwekukuvadza kweTP53 muhuwandu hwevanhu hahuzivikanwe, uye kuitika kwechokwadi kweFSS hakuzivikanwi. Inofungidzira inopesana pakati pe1 kubva kune 5 000 uye 1 mu20,000. Sezvo dzimwe mhuri dzinoenda kuongororwa kwe TP53, kupararira kwechokwadi kweLFS kunogona kujeka.
Kutaura nezveHuman Breast Risk
MuUnited States, National Comprehensive Cancer Network (NCCN) anorayira kupa gore reMRI chiremba kwemakore makumi maviri nemakumi maviri nemakumi maviri nemakore egore reMRI uye mammography kubva pamakore makumi matatu kusvika kune makumi matatu. MuAustralia, mitemo yenyika inokurudzira kuti mastectomy yakawanda inofanira kupiwa, zvisinei gore regore rinonzi MRI rinokurudzirwa kubva pamakore makumi maviri nemashanu. Schon uye vashandi vanokurudzira kuti sarudzo yekutengesa-kuderedza mastectomy yepakati pemagetsi kana kuongorora mazamu kunofanira kuonekwa mumadzimai asina kenza ine kuchinja mumutambo we TP53 .
NCCN Zvirongwa
Kubva pakutsvaga kuti njodzi yekenza yemwana inowedzera zvakanyanya mushure memakore gumi nemaviri, mazano akaratidza kuti kuwirirana kwepachiviri chetachiona kunofanira kuonekwa kubva kune makore makumi maviri. Gore rinopera kenza yepabonde rinowedzera kusvika pamakore makumi mana kusvika makumi mashanu nemakumi mana nemashanu uye rinoderera, zvakadai kuti mastectomy zvishoma kubatsira vakadzi vanopfuura makore makumi matanhatu.
- Kuziva mazamu, kutanga pamakore gumi nemasere, ne periodic, nguva dzose mazamu anozviongorora.
- Clinical breast test, mwedzi mitanhatu kusvika ku12, kutanga pamakore makumi maviri
- Zera 20-29 makore, gore rega pachipfu MRI kuongorora nekusiyana
- Makore 30-75 emakore, gore rega pachipfu MRI kuongorora nekusiyana uye mammogram nekufungisisa kweTomosynthesis
- Zera> makore makumi manomwe, vatungamiri vanofanira kuonekwa semunhu mumwechete.
- Kune vakadzi vane mutsika weTP53 avo vanorapwa nekenza yemucheche, uye vasina kumbova nemararamiro ehurumende, kuongorora gore negore MRI uye mammogram inofanira kuenderera mberi sezvinotsanangurwa pamusoro apa.
- Kana chisarudzo chekuisa pangozi-kuderedza mastectomi inokurukurwa, panofanira kunge kune mazano maererano nehuwandu hwekuchengetedzwa, dhigirii rezera rekare rinokonzerwa nekenza, maitiro ekuvakazve, uye kukonzera kukanganisa kwevamwe kanzira. Maonero ehupenyu, hutano, uye hutano hwehupenyu hwehupenyu hwehutachiona hwekuchera mastectomy hunofanira kuiswa munhaurirano dzakadaro.
Kutaura Neimwe Mungozi yeCancer
NCCN Zvirongwa
- Kuongorora kwakakwana mumuviri kunosanganisira kuongororwa neurologic nehuwandu hwekunyunyuta kwevana vashoma vanorwisa uye maronda echipiri muvanopukunyuka chirwere mumwedzi 6-12.
- Colonoscopy nepamusoro endoscopy makore maviri kusvika ku5 kubva pazera remakore makumi maviri nemashanu kana makore mashanu musati yatozivikanwa kare kanaroni yekoloni mumhuri (chero ipi inouya pakutanga).
- Gore negore dermatologic test inotangira pamakore gumi nemana.
- Gore negore muviri wose MRI
- Uropi hwegore negore MRI inogona kuitwa sechikamu chemuviri weMRI kana sekuongorora kwakasiyana.
Mamwe mafomu ekuongorora uye kuongororwa
Paiva nemhosva yekupayisa ye positron emission tomography (FDG-PET) / CT maonero kuvanhu vakuru vane LFS vakaona tumarara mumatatu evanhu 15. Izvi zvinongororwa nePET-CT, kunyange zvazvo zvakakosha pakuwana mamwe maronda, uyewo inowedzera kupisa kwemaawa nguva dzose pavanenge vapedza, uye saka nzira iyi yekutsvaga yakagadziriswa uye yakashandurwa ku muviri wose weMRI kuvanhu vakuru vane TP53 zvakasiyana-siyana.
Mitsva yakawanda yekutsvakurudza yakatanga kushandura chirongwa chakasimba chekuongororwa chinosanganisira nokukurumidza muviri wose weMRI, uropi MRI, chibereko chemuviri chekuongorora, uye yekuongorora maitiro eAdrenal cortical basa. Rudzi urwu rwekucherechedza runogona kuwedzera kupona kwevanhu vane LFS nekuona zvirwere zvisati zvave nezviratidzo, asi zvimwe zvidzidzo zvinodiwa kuratidza kuti rudzi urwu rwehurumende runoshanda kune vanhu vakuru nevana vane LFS.
Vanhu vane LFS vakabvunzwa nezvemaonero avo nezvekenza kuongororwa, uye vazhinji vanoita sevanotenda mukukosha kwekuongororwa kuti vaone tumarara mumatambo ekutanga. Vakataurawo pfungwa yekudzivirira uye kuchengetedzwa kunobatanidza nekubatanidzwa mune imwe chirongwa chekucherechedza
Kuedza Vana kune TP53 Mutations
Zvinokwanisika kuedza vana nevechiri kuyaruka nekuda kwekuchinja kwekuchinja kweLFS, asi kunetseka kwakakurudzirwa pamusoro pezvingangova nengozi, zvikomborero, nekugadziriswa kwekuita kudaro, kusanganisira kusashaiwa kwekuongororwa kunoratidzwa kana maitiro ekudzivirira, uye kunetseka pamusoro pekushorwa nekusarurwa.
Zvakakurudzirwa kuti kuongororwa vanhu vaduku vaduku kune makore gumi nematanhatu kuti TP53 pathogenic variko zviitwe mukati megurogiramu inopa zvose ma-test-test uye pashure pekuedzwa kwemashoko nekupa mazano.
> Sources:
> Ballinger ML, Best A, Mai PL, et al. Baseline kuongororwa muLi-Fraumeni syndrome vachishandisa muviri wose-magnetic resonance imaging: meta-analysis [yakabudiswa paIndaneti August 3, 2017]. JAMA Oncol.
> Correa H. Li-Fraumeni Syndrome. J Pediatr Genet. 2016; 5 (2): 84-88.
> Katherine Schon naMarc Tischkowitz. Chirongwa chemakemikari chinokonzerwa nekuchinja kwegermine mukenza yebonde: TP53. Chirwere chepabonde Res Treat. 2018; 167 (2): 417-423.
> Mai PL, Best AF, Peters JA, et al. Ngozi dzekenza yekutanga neyekupedzisira pakati pe TP53 mutsika-vatakuri muCII LFS boka. Cancer . 2016; 122 (23): 3673-3681.
> NCCN kliniki yekuita mirayiridzo muoncology 1.2018 - Gumiguru 3, 2017: Jenethi / mhuri yepamusoro-kutarisa kuongorora: mazamu uye ovarian. NCCN Clinical Practice Guidelines: http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf.
> Tinat J, Bougeard G, Baert-Desurmont S, et al. 2009 version ye Chompret yemirairo yeLi Fraumeni syndrome . J Clin Oncol. 2009; 27 (26): e108-9.