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Test genetico per la predisposizione del tumore al colon

15MAR2017
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ColonScreen® è un test diagnostico ,  che permette di  eseguire  un’analisi genetica multipla  per valutare la predisposizione allo sviluppo del tumore al Colon-retto o della Poliposi Adenomatosa Familiare. Il test, quindi, permette di identificare  i  pazienti a rischio di insorgenza delle suddette neoplasie attraverso l’analisi del loro DNA.

Il test di predisposizione genetica è indirizzato a quelle persone che ad una approfondita anamnesi familiare risultano con elevata e specifica incidenza di malattie neoplastiche nelle generazioni precedenti, e pertanto ad elevato rischio di essere portatori di mutazione germinale.

Si può sospettare una forma ereditaria di neoplasia quando in una famiglia vi sono:
• diversi soggetti affetti dallo stesso tipo di tumore o tumori correlati,
• soggetti affetti da tumori multipli,
• tumori insorti in età giovanile.

In particolare:
• Tumore colon-rettale diagnosticato ≤ 50 anni;
• Tumori all’utero od ovarici con una storia familiare di tumori gastrointestinali;
• Soggetti con più di un tumore associato a Sindrome di Lynch (es. tumore colon-rettale ed uterino);
• Tre o più casi in famiglia di tumore colon-rettale, ovarico, uterino, gastrico o altri tumori associati a Sindrome di Lynch;
• Risultati del test di instabilità dei Microsatelliti o di immonoistochimica nel tumore indicanti una ridotta capacità di riparazione degli errori di replicazione del DNA;
• Tumori primari multipli nello stesso paziente;
• Più membri della famiglia (sullo stesso lato) con tumore colon-rettale o altri tipi di tumore.
• Una mutazione nota in famiglia in uno dei geni associati alla predisposizione ai tumori colon-rettali / poliposi familiare

Come si effettua

Il test ColonScreen® viene eseguito mediante il prelievo di un campione ematico. Tramite un’analisi complessa di laboratorio, Il DNA viene isolato dalle cellule nucleate ed amplificato mediante tecnica PCR. Successivamente, attraverso un processo tecnologico avanzato di sequenziamento massivo parallelo (MPS), che impiega tecniche di Next Generation Sequencing (NGS) utilizzando sequenziatori ILLUMINA, si sequenziano completamente, ad elevata profondità di lettura, 12 geni (esoni e regioni introniche adiacenti, ± 5 nucleotidi – vedasi Tabella 1) coinvolti nella maggior parte dei casi di predisposizione ereditaria allo sviluppo del tumore al Colon-retto o della Poliposi Adenomatosa Familiare. Le sequenze geniche ottenute vengono analizzate attraverso un’avanzata analisi bioinformatica, per determinare la presenza di eventuali mutazioni nei geni in esame.

Benefici del test

La possibilità di individuare i soggetti a rischio di sviluppare una neoplasia rappresenta oggi il miglior metodo per giungere ad una diagnosi precoce del tumore e quindi per ridurre la mortalità in tale patologia.
I membri di famiglie ad alto rischio ereditario, ed in particolare chi è stato interessato direttamente da una neoplasia, può richiedere una consulenza genetica e discutere con il genetista circa la propria situazione clinico-genetica. Tale valutazione potrà promuovere il test genetico per accertare se il paziente è portatore di una mutazione che predispone allo sviluppo di un tumore specifico.
In caso di positività del test l’accertamento potrà essere esteso ai familiari del paziente, al fine di individuare i soggetti a rischio.

L’informazione ottenuta dal test genetico può apportare notevoli benefici, quali:

  • l’identificazione dei membri di una famiglia che sono ad alto rischio di sviluppare il tumore;
  • l’organizzazione di un adeguato programma di controllo medico riservato ai soggetti ad alto rischio, in maniera tale da facilitare la diagnosi precoce all’insorgenza del tumore;
  • la conoscenza della possibilità di trasmissione delle mutazioni geniche alla progenie e l’individuazione dei soggetti figli, con mutazioni geniche germinali, ad alto rischio;
  • la valutazione di eventuali indicazioni a terapie di profilassi preventiva.

 

Risultati del test
POSITIVO : Presenza di una o più mutazioni:
indica che il test ha rilevato una o più mutazioni a livello di uno (o più) gene responsabile della predisposizione ereditaria allo sviluppo tumore del tumore al Colon-retto o della Poliposi Adenomatosa Familiare, cioè presentano una copia del gene mutata. Il nostro genetista, in sede di consulenza genetica, spiegherà in maniera dettagliata il significato del risultato del test, fornendo una stima in termini probabilistici riguardo il rischio di sviluppare il tumore specifico, associato a quel tipo di mutazione riscontrata in un particolare gene.

NEGATIVO: Assenza di mutazioni:
indica che il test non ha rilevato la presenza di mutazioni nei geni esaminati. Tuttavia è importante sottolineare che un risultato negativo non significa che il paziente ha rischio zero di sviluppare un tumore; queste persone possiedono lo stesso rischio di tumore riportato per la popolazione generale.

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