Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma.

Autor:	Grande BM; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Gerhard DS; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Jiang A; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Griner NB; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Abramson JS; Center for Lymphoma, Massachusetts General Hospital, Harvard Medical School, Boston, MA., Alexander TB; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN., Allen H; Nationwide Children's Hospital, Columbus, OH., Ayers LW; Department of Pathology, The Ohio State University, Columbus, OH., Bethony JM; George Washington University, Washington, DC., Bhatia K; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD., Bowen J; Nationwide Children's Hospital, Columbus, OH., Casper C; Infectious Disease Research Institute, Seattle, WA., Choi JK; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN., Culibrk L; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Davidsen TM; Cancer Informatics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Dyer MA; Clinical Research Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD., Gastier-Foster JM; Nationwide Children's Hospital, Columbus, OH.; Departments of Pathology and Pediatrics, The Ohio State University, Columbus, OH., Gesuwan P; Cancer Informatics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Greiner TC; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE., Gross TG; Center for Global Health, National Cancer Institute, National Institutes of Health, Rockville, MD., Hanf B; Nationwide Children's Hospital, Columbus, OH., Harris NL; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA., He Y; Cancer Informatics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Irvin JD; Foundation for Burkitt Lymphoma Research, Geneva, Switzerland., Jaffe ES; Laboratory of Pathology, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD., Jones SJM; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Kerchan P; EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda., Knoetze N; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Leal FE; Programa de Oncovirologia, Instituto Nacional de Câncer José de Alencar, Rio de Janeiro, Brazil., Lichtenberg TM; Nationwide Children's Hospital, Columbus, OH., Ma Y; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Martin JP; Foundation for Burkitt Lymphoma Research, Geneva, Switzerland., Martin MR; Foundation for Burkitt Lymphoma Research, Geneva, Switzerland., Mbulaiteye SM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD., Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Namirembe C; Uganda Cancer Institute, Kampala, Uganda., Novik K; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Noy A; Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Cornell Medical College, New York, NY., Ogwang MD; EMBLEM Study, St. Mary's Hospital Lacor, Gulu, Uganda., Omoding A; Uganda Cancer Institute, Kampala, Uganda., Orem J; Uganda Cancer Institute, Kampala, Uganda., Reynolds SJ; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and., Rushton CK; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Sandlund JT; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN., Schmitz R; Lymphoid Malignancies Branch, Center for Cancer Research and., Taylor C; Nationwide Children's Hospital, Columbus, OH., Wilson WH; Lymphoid Malignancies Branch, Center for Cancer Research and., Wright GW; Biometric Research Program, Division of Cancer Diagnosis and Treatment, National Cancer Institute, National Institutes of Health, Rockville, MD., Zhao EY; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Marra MA; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Morin RD; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.; Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada., Staudt LM; Lymphoid Malignancies Branch, Center for Cancer Research and.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2019 Mar 21; Vol. 133 (12), pp. 1313-1324. Date of Electronic Publication: 2019 Jan 07.
DOI:	10.1182/blood-2018-09-871418
Abstrakt:	Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A , USP7 , and CHD8 , we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients. (© 2019 by The American Society of Hematology.)
Databáze:	MEDLINE
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