Research Papers:

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin’s lymphoma

Valli De Re _, Laura Caggiari, Lara Mussolin, Emanuele Stefano d’Amore, Barbara Famengo, Mariangela De Zorzi, Lia Martina, Caterina Elia, Marta Pillon, Nicola Santoro, Paola Muggeo, Salvatore Buffardi, Maurizio Bianchi, Alessandra Sala, Piero Farruggia, Luciana Vinti, Edgardo D. Carosella, Roberta Burnelli and Maurizio Mascarin

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Oncotarget. 2017; 8:105957-105970. https://doi.org/10.18632/oncotarget.22515

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Valli De Re1,*, Laura Caggiari1,*, Lara Mussolin2,**, Emanuele Stefano d’Amore3,**, Barbara Famengo3,**, Mariangela De Zorzi1, Lia Martina1, Caterina Elia4, Marta Pillon5,**, Nicola Santoro6,**, Paola Muggeo6,**, Salvatore Buffardi7,**, Maurizio Bianchi8,**, Alessandra Sala9,**, Piero Farruggia10,**, Luciana Vinti11,**, Edgardo D. Carosella12, Roberta Burnelli13,** and Maurizio Mascarin4,**

1Immunopathology and Cancer Biomarkers, Department of Translational Research, CRO Aviano National Cancer Institute, Aviano, Italy

2Clinic of Pediatric Hemato-Oncology, Department of Women’s and Children’s Health, University of Padova, Institute of Paediatric Research Fondazione Città della Speranza, Padova, Italy

3Department of Pathology, San Bortolo Hospital, Vicenza, Italy

4Pediatric Radiotherapy Unit, CRO Aviano National Cancer Institute, Aviano, Italy

5Clinic of Paediatric Hemato-Oncology, Department of Women’s and Children’s Health, University of Padova, Padova, Italy

6Department of Paediatric Hemato-Oncology, University of Bari, Bari, Italy

7Department of Paediatric Hemato-Oncology, Santobono-Pausilipon Children’s Hospital, Napoli, Italy

8Department of Paediatric Hemato-Oncology, Regina Margherita Children’s Hospital, Torino, Italy

9Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy

10Pediatric Hematology and Oncology Unit, Oncology Department, A.R.N.A.S. Ospedali Civico, Di Cristina e Benfratelli, Palermo, Italy

11Department of Paediatric Hemato-Oncology, IRCCS Ospedale Bambino Gesù, Roma, Italy

12Department of Hemato-Immunological Research, Institut des Maladies Emergentes et des Thérapies Innovantes (iMETI), Hôpital Saint Louis, Paris, France

13Pediatric Hematology-Oncology, Azienda Ospedaliera Universitaria, Ospedale Sant’Anna, Ferrara, Italy

*These authors have contributed equally to this work

**These authors are members of the AIEOP group

Correspondence to:

Valli De Re, email: [email protected]

Keywords: pediatric hodgkin lymphoma; HLA-G; event-free survival; 3’UTR polymorphism; +3027 C/A genotype

Received: July 21, 2017    Accepted: October 28, 2017    Published: November 18, 2017


In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin’s lymphoma (HL). We evaluated the association of HLA-G 3’-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

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