Skip to main content
Top
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

EP300 single nucleotide polymorphism rs20551 correlates with prolonged overall survival in diffuse large B cell lymphoma patients treated with R-CHOP

Authors: Jiao Li, Ning Ding, Xiaogan Wang, Lan Mi, Lingyan Ping, Xuan Jin, Yalu Liu, Zhitao Ying, Yan Xie, Weiping Liu, Yuqin Song, Jun Zhu

Published in: Cancer Cell International | Issue 1/2017

Login to get access

Abstract

Background

Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown.

Methods

In this study we analyzed the EP300 SNP rs20551 and prognosis of 226 DLBCL patients who treated with R-CHOP or R-CHOP-like regimes from 2002 to 2013. Determination of the EP300 SNP rs20551 from genomic DNA was obtained by Sanger chain termination sequencing.

Result

In this study, the frequency of the A and G allele of the EP300 SNP rs20551 in 226 patients were 92.5 and 7.5%, respectively. We did not observe obvious correlation between patients’ disease features and the EP300 SNP rs20551. But the patients with genotype AA had a higher 5-year overall survival rate than those with genotype GA (77.0% vs. 64.7%, p = 0.045). Furthermore, multivariate Cox regression analysis showed that the GA genotype of EP300 SNP rs20551 was an independent poor prognostic factor for DLBCL patients treated with Rituximab-chemotherapy (p = 0.009, HR 2.956, 95% CI 1.315–6.645).

Conclusion

This study suggests that EP300 SNP rs20551 might be a useful biomarker to predict the long-term outcome of R-CHOP in DLBCL patients.
Literature
1.
go back to reference Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.CrossRefPubMed Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.CrossRefPubMed
2.
go back to reference Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Grouped’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–5.CrossRefPubMedPubMedCentral Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Grouped’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–5.CrossRefPubMedPubMedCentral
3.
go back to reference Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20 + B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9(2):105–16.CrossRefPubMed Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20 + B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9(2):105–16.CrossRefPubMed
4.
go back to reference Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O’Reilly S, Spinelli JJ, Sutherland J, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027–33.CrossRefPubMed Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O’Reilly S, Spinelli JJ, Sutherland J, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027–33.CrossRefPubMed
5.
go back to reference Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121–7.CrossRefPubMed Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121–7.CrossRefPubMed
6.
go back to reference Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematol Am Soc Hematol Educ Progr. 2011;2011:498–505. Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematol Am Soc Hematol Educ Progr. 2011;2011:498–505.
7.
go back to reference Rossi G, Donisi A, Casari S, Re A, Cadeo G, Carosi G. The International Prognostic Index can be used as a guide to treatment decisions regarding patients with human immunodeficiency virus-related systemic non-Hodgkin lymphoma. Cancer. 1999;86(11):2391–7.CrossRefPubMed Rossi G, Donisi A, Casari S, Re A, Cadeo G, Carosi G. The International Prognostic Index can be used as a guide to treatment decisions regarding patients with human immunodeficiency virus-related systemic non-Hodgkin lymphoma. Cancer. 1999;86(11):2391–7.CrossRefPubMed
8.
go back to reference Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996;87(5):953–9.CrossRefPubMed Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996;87(5):953–9.CrossRefPubMed
9.
go back to reference Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996;384(6610):641–3.CrossRefPubMed Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996;384(6610):641–3.CrossRefPubMed
10.
go back to reference Brook CL, Gu W. The impact of acetylation and deacetylation on the p53 pathway. Protein Cell. 2011;2(6):456–62.CrossRef Brook CL, Gu W. The impact of acetylation and deacetylation on the p53 pathway. Protein Cell. 2011;2(6):456–62.CrossRef
11.
go back to reference Shigeno K, Yoshida H, Pan L, Luo JM, Fujisawa S, Naito K, Nakamura S, Shinjo K, Takeshita A, Ohno R, et al. Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias. Cancer Lett. 2004;213(1):11–20.CrossRefPubMed Shigeno K, Yoshida H, Pan L, Luo JM, Fujisawa S, Naito K, Nakamura S, Shinjo K, Takeshita A, Ohno R, et al. Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias. Cancer Lett. 2004;213(1):11–20.CrossRefPubMed
12.
go back to reference Fergelot P, Van Belzen M, Van Gils J, Afenjar A, Armour CM, Arveiler B, Beets L, Burglen L, Busa T, Collet M, et al. Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations. Am J Med Genet Part A. 2016;170(12):3069–82.CrossRefPubMed Fergelot P, Van Belzen M, Van Gils J, Afenjar A, Armour CM, Arveiler B, Beets L, Burglen L, Busa T, Collet M, et al. Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations. Am J Med Genet Part A. 2016;170(12):3069–82.CrossRefPubMed
13.
go back to reference Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature. 1995;374(6517):81–4.CrossRefPubMed Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature. 1995;374(6517):81–4.CrossRefPubMed
14.
go back to reference Lundblad JR, Kwok RP, Laurance ME, Harter ML, Goodman RH. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature. 1995;374(6517):85–8.CrossRefPubMed Lundblad JR, Kwok RP, Laurance ME, Harter ML, Goodman RH. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature. 1995;374(6517):85–8.CrossRefPubMed
15.
go back to reference Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y. Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13). Blood. 1997;90(12):4699–704.PubMed Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y. Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13). Blood. 1997;90(12):4699–704.PubMed
16.
go back to reference Muraoka M, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Shitara N, Chong JM, Iwama T, Miyaki M. p300 gene alterations in colorectal and gastric carcinomas. Oncogene. 1996;12(7):1565–9.PubMed Muraoka M, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Shitara N, Chong JM, Iwama T, Miyaki M. p300 gene alterations in colorectal and gastric carcinomas. Oncogene. 1996;12(7):1565–9.PubMed
17.
go back to reference Giles RH, Peters DJ, Breuning MH. Conjunction dysfunction: CBP/p300 in human disease. Trends Genet. 1998;14(5):178–83.CrossRefPubMed Giles RH, Peters DJ, Breuning MH. Conjunction dysfunction: CBP/p300 in human disease. Trends Genet. 1998;14(5):178–83.CrossRefPubMed
18.
go back to reference Borrow J, Stanton VP Jr, Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dubé I, Frischauf AM, et al. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet. 1996;14(1):33–41.CrossRefPubMed Borrow J, Stanton VP Jr, Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dubé I, Frischauf AM, et al. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet. 1996;14(1):33–41.CrossRefPubMed
19.
go back to reference Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011;471(7337):189–95.CrossRefPubMedPubMedCentral Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011;471(7337):189–95.CrossRefPubMedPubMedCentral
21.
go back to reference Weaver BK, Kumar KP, Reich NC. Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol Cell Biol. 1998;18(3):1359–68.CrossRefPubMedPubMedCentral Weaver BK, Kumar KP, Reich NC. Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol Cell Biol. 1998;18(3):1359–68.CrossRefPubMedPubMedCentral
22.
go back to reference Liu X, Wang L, Zhao K, Thompson PR, Hwang Y, Marmorstein R, Cole PA. The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature. 2008;451(7180):846–50.CrossRefPubMed Liu X, Wang L, Zhao K, Thompson PR, Hwang Y, Marmorstein R, Cole PA. The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature. 2008;451(7180):846–50.CrossRefPubMed
23.
go back to reference Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin SF, Daigo Y, Russell P, Wilson A, Sowter HM, et al. Mutations truncating the EP300 acetylase in human cancers. Nat Genet. 2000;24(3):300–3.CrossRefPubMed Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin SF, Daigo Y, Russell P, Wilson A, Sowter HM, et al. Mutations truncating the EP300 acetylase in human cancers. Nat Genet. 2000;24(3):300–3.CrossRefPubMed
24.
go back to reference Phan RT, Dalla-Favera R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature. 2004;432(7017):635–9.CrossRefPubMed Phan RT, Dalla-Favera R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature. 2004;432(7017):635–9.CrossRefPubMed
25.
go back to reference Phan RT, Saito M, Basso K, Niu H, Dalla-Favera R. BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat Immunol. 2005;6(10):1054–60.CrossRefPubMed Phan RT, Saito M, Basso K, Niu H, Dalla-Favera R. BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat Immunol. 2005;6(10):1054–60.CrossRefPubMed
26.
go back to reference Piwkham D, Gelfond JA, Rerkamnuaychoke B, Pakakasama S, Rebel VI, Pollock BH, Winick NJ, Collier AB 3rd, Tomlinson GE, Beuten J. Multilocus association of genetic variants in MLL, CREBBP, EP300, and TOP2A with childhood acute lymphoblastic leukemia in Hispanics from Texas. Cancer Epidemiol Biomark Prev. 2011;20(6):1204–12.CrossRef Piwkham D, Gelfond JA, Rerkamnuaychoke B, Pakakasama S, Rebel VI, Pollock BH, Winick NJ, Collier AB 3rd, Tomlinson GE, Beuten J. Multilocus association of genetic variants in MLL, CREBBP, EP300, and TOP2A with childhood acute lymphoblastic leukemia in Hispanics from Texas. Cancer Epidemiol Biomark Prev. 2011;20(6):1204–12.CrossRef
27.
go back to reference Martín-Antonio B, Álvarez-Laderas I, Cardesa R, Márquez-Malaver F, Baez A, Carmona M, Falantes J, Suarez-Lledo M, Fernández-Avilés F, Martínez C, et al. A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT. Bone Marrow Transpl. 2012;47(9):1206–11.CrossRef Martín-Antonio B, Álvarez-Laderas I, Cardesa R, Márquez-Malaver F, Baez A, Carmona M, Falantes J, Suarez-Lledo M, Fernández-Avilés F, Martínez C, et al. A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT. Bone Marrow Transpl. 2012;47(9):1206–11.CrossRef
28.
go back to reference Goodman RH, Smolik S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 2000;14(13):1553–77.PubMed Goodman RH, Smolik S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 2000;14(13):1553–77.PubMed
29.
go back to reference Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90(4):595–606.CrossRefPubMed Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90(4):595–606.CrossRefPubMed
31.
go back to reference Vervoorts J, Lüscher-Firzlaff JM, Rottmann S, Lilischkis R, Walsemann G, Dohmann K, Austen M, Lüscher B. Stimulation of c-MYC transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Rep. 2003;4(5):484–90.CrossRefPubMedPubMedCentral Vervoorts J, Lüscher-Firzlaff JM, Rottmann S, Lilischkis R, Walsemann G, Dohmann K, Austen M, Lüscher B. Stimulation of c-MYC transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Rep. 2003;4(5):484–90.CrossRefPubMedPubMedCentral
32.
go back to reference Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, et al. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin’s lymphoma and mantle cell lymphoma. J Clin Oncol. 2011;29(9):1198–203.CrossRefPubMedPubMedCentral Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, et al. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin’s lymphoma and mantle cell lymphoma. J Clin Oncol. 2011;29(9):1198–203.CrossRefPubMedPubMedCentral
33.
go back to reference Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, et al. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016;128(2):185–94.CrossRefPubMedPubMedCentral Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, et al. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016;128(2):185–94.CrossRefPubMedPubMedCentral
34.
go back to reference Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, et al. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014;165(6):768–76.CrossRefPubMedPubMedCentral Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, et al. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014;165(6):768–76.CrossRefPubMedPubMedCentral
Metadata
Title
EP300 single nucleotide polymorphism rs20551 correlates with prolonged overall survival in diffuse large B cell lymphoma patients treated with R-CHOP
Authors
Jiao Li
Ning Ding
Xiaogan Wang
Lan Mi
Lingyan Ping
Xuan Jin
Yalu Liu
Zhitao Ying
Yan Xie
Weiping Liu
Yuqin Song
Jun Zhu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0439-1

Other articles of this Issue 1/2017

Cancer Cell International 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine