A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma.

Autor:	Mirabello L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. mirabellol@mail.nih.gov., Koster R; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Moriarity BS; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota. Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota., Spector LG; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota., Meltzer PS; Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland., Gary J; Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda, Maryland; College of Veterinary Medicine, Michigan State University, East Lansing, Michigan., Machiela MJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Pankratz N; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota., Panagiotou OA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Largaespada D; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota. Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota., Wang Z; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Gastier-Foster JM; Nationwide Children's Hospital, and The Ohio State University Department of Pathology and Pediatrics, Columbus, Ohio., Gorlick R; Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, New York., Khanna C; Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland., de Toledo SR; Pediatric Oncology Institute, GRAACC/UNIFESP, São Paulo SP, Brazil., Petrilli AS; Pediatric Oncology Institute, GRAACC/UNIFESP, São Paulo SP, Brazil., Patiño-Garcia A; Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain., Sierrasesúmaga L; Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain., Lecanda F; Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain., Andrulis IL; University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada., Wunder JS; University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada., Gokgoz N; University of Toronto, Litwin Centre for Cancer Genetics, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada., Serra M; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Hattinger C; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Picci P; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Scotlandi K; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Flanagan AM; University College London Cancer Institute, London, United Kingdom. Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, Middlesex, United Kingdom., Tirabosco R; Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, Middlesex, United Kingdom., Amary MF; Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, Middlesex, United Kingdom., Halai D; Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, Middlesex, United Kingdom., Ballinger ML; Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia., Thomas DM; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Davis S; Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland., Barkauskas DA; Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California., Marina N; Stanford University and Lucile Packard Children's Hospital, Palo Alto, California., Helman L; Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland., Otto GM; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota., Becklin KL; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota., Wolf NK; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota., Weg MT; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota., Tucker M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Wacholder S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Fraumeni JF Jr; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Caporaso NE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Boland JF; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Hicks BD; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Vogt A; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Burdett L; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Yeager M; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Hoover RN; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland., Savage SA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2015 Sep; Vol. 5 (9), pp. 920-31. Date of Electronic Publication: 2015 Jun 17.
DOI:	10.1158/2159-8290.CD-15-0125
Abstrakt:	Unlabelled: Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 × 10(-9); OR, 2.43; 95% confidence interval, 1.83-3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene. Significance: Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the NFIB locus as associated with metastatic potential in osteosarcoma. (©2015 American Association for Cancer Research.)
Databáze:	MEDLINE
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