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

Lisa Giulino-Roth; Kai Wang; Theresa Y. MacDonald; Susan Mathew; Yifang Tam; Maureen T. Cronin; Gary Palmer; Norma Lucena-Silva; Francisco Pedrosa; Marcia Pedrosa; Julie Teruya-Feldstein; Govind Bhagat; Bachir Alobeid; Lorenzo Leoncini; Cristiana Bellan; Emily Rogena; Kerice A. Pinkney; Mark A. Rubin; Raul C. Ribeiro; Roman Yelensky; Wayne Tam; Philip J. Stephens; Ethel Cesarman

doi:10.1182/blood-2012-06-437624

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

Lisa Giulino-Roth, Kai Wang, Theresa Y. MacDonald, Susan Mathew, Yifang Tam, Maureen T. Cronin, Gary Palmer, Norma Lucena-Silva, Francisco Pedrosa, Marcia Pedrosa, Julie Teruya-Feldstein, Govind Bhagat, Bachir Alobeid, Lorenzo Leoncini, Cristiana Bellan, Emily Rogena, Kerice A. Pinkney, Mark A. Rubin, Raul C. Ribeiro, Roman YelenskyWayne Tam, Philip J. Stephens, Ethel Cesarman

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

Abstract

To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded 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 tohave multiple mutations (P < .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 roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.

Original language	English
Pages (from-to)	5181-5184
Number of pages	4
Journal	Blood
Volume	120
Issue number	26
DOIs	https://doi.org/10.1182/blood-2012-06-437624
State	Published - 20 Dec 2012
Externally published	Yes

Access to Document

10.1182/blood-2012-06-437624

Cite this

Giulino-Roth, L., Wang, K., MacDonald, T. Y., Mathew, S., Tam, Y., Cronin, M. T., Palmer, G., Lucena-Silva, N., Pedrosa, F., Pedrosa, M., Teruya-Feldstein, J., Bhagat, G., Alobeid, B., Leoncini, L., Bellan, C., Rogena, E., Pinkney, K. A., Rubin, M. A., Ribeiro, R. C., ... Cesarman, E. (2012). Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes. Blood, 120(26), 5181-5184. https://doi.org/10.1182/blood-2012-06-437624

@article{08fa35e13c474b63ad561c4d8234bd6c,

title = "Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes",

abstract = "To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded 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 tohave multiple mutations (P < .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 roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.",

author = "Lisa Giulino-Roth and Kai Wang and MacDonald, {Theresa Y.} and Susan Mathew and Yifang Tam and Cronin, {Maureen T.} and Gary Palmer and Norma Lucena-Silva and Francisco Pedrosa and Marcia Pedrosa and Julie Teruya-Feldstein and Govind Bhagat and Bachir Alobeid and Lorenzo Leoncini and Cristiana Bellan and Emily Rogena and Pinkney, {Kerice A.} and Rubin, {Mark A.} and Ribeiro, {Raul C.} and Roman Yelensky and Wayne Tam and Stephens, {Philip J.} and Ethel Cesarman",

year = "2012",

month = dec,

day = "20",

doi = "10.1182/blood-2012-06-437624",

language = "English",

volume = "120",

pages = "5181--5184",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier BV",

number = "26",

}

Giulino-Roth, L, Wang, K, MacDonald, TY, Mathew, S, Tam, Y, Cronin, MT, Palmer, G, Lucena-Silva, N, Pedrosa, F, Pedrosa, M, Teruya-Feldstein, J, Bhagat, G, Alobeid, B, Leoncini, L, Bellan, C, Rogena, E, Pinkney, KA, Rubin, MA, Ribeiro, RC, Yelensky, R, Tam, W, Stephens, PJ & Cesarman, E 2012, 'Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes', Blood, vol. 120, no. 26, pp. 5181-5184. https://doi.org/10.1182/blood-2012-06-437624

TY - JOUR

T1 - Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes

AU - Giulino-Roth, Lisa

AU - Wang, Kai

AU - MacDonald, Theresa Y.

AU - Mathew, Susan

AU - Tam, Yifang

AU - Cronin, Maureen T.

AU - Palmer, Gary

AU - Lucena-Silva, Norma

AU - Pedrosa, Francisco

AU - Pedrosa, Marcia

AU - Teruya-Feldstein, Julie

AU - Bhagat, Govind

AU - Alobeid, Bachir

AU - Leoncini, Lorenzo

AU - Bellan, Cristiana

AU - Rogena, Emily

AU - Pinkney, Kerice A.

AU - Rubin, Mark A.

AU - Ribeiro, Raul C.

AU - Yelensky, Roman

AU - Tam, Wayne

AU - Stephens, Philip J.

AU - Cesarman, Ethel

PY - 2012/12/20

Y1 - 2012/12/20

N2 - To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded 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 tohave multiple mutations (P < .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 roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.

AB - To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded 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 tohave multiple mutations (P < .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 roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.

UR - http://www.scopus.com/inward/record.url?scp=84871498761&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-06-437624

DO - 10.1182/blood-2012-06-437624

M3 - Article

C2 - 23091298

AN - SCOPUS:84871498761

SN - 0006-4971

VL - 120

SP - 5181

EP - 5184

JO - Blood

JF - Blood

IS - 26

ER -

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

Abstract

Access to Document

Fingerprint

Cite this