To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL) we performed clinical-grade next generation sequencing (NGS) of 189 cancer-related genes on 29 formalin-fixed paraffin embedded (FFPE) primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations (p<0.0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the role of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.

Giulino Roth, L., Wang, K., Macdonald, T.y., Mathew, S., Tam, Y., Cronin, M.t., et al. (2012). Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in anti-apoptotic and chromatin-remodeling genes. BLOOD, 120(26), 5181-5184 [10.1182/blood-2012-06-437624].

Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in anti-apoptotic and chromatin-remodeling genes.

LEONCINI, LORENZO;BELLAN, CRISTIANA;
2012

Abstract

To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL) we performed clinical-grade next generation sequencing (NGS) of 189 cancer-related genes on 29 formalin-fixed paraffin embedded (FFPE) primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations (p<0.0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the role of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.
File in questo prodotto:
File Dimensione Formato  
Blood 2012 Giulino Roth et al.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 366.4 kB
Formato Adobe PDF
366.4 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/40561
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo