Genome-wide association study identifies two susceptibility loci for osteosarcoma

Sharon A. Savage; Lisa Mirabello; Zhaoming Wang; Julie M. Gastier-Foster; Richard Gorlick; Chand Khanna; Adrienne M. Flanagan; Roberto Tirabosco; Irene L. Andrulis; Jay S. Wunder; Nalan Gokgoz; Ana Patiño-Garcia; Luis Sierrasesúmaga; Fernando Lecanda; Nilgün Kurucu; Inci Ergurhan Ilhan; Neriman Sari; Massimo Serra; Claudia Hattinger; Piero Picci; Logan G. Spector; Donald A. Barkauskas; Neyssa Marina; Silvia Regina Caminada De Toledo; Antonio S. Petrilli; Maria Fernanda Amary; Dina Halai; David M. Thomas; Chester Douglass; Paul S. Meltzer; Kevin Jacobs; Charles C. Chung; Sonja I. Berndt; Mark P. Purdue; Neil E. Caporaso; Margaret Tucker; Nathaniel Rothman; Maria Teresa Landi; Debra T. Silverman; Peter Kraft; David J. Hunter; Nuria Malats; Manolis Kogevinas; Sholom Wacholder; Rebecca Troisi; Lee Helman; Joseph F. Fraumeni; Meredith Yeager; Robert N. Hoover; Stephen J. Chanock

doi:10.1038/ng.2645

Genome-wide association study identifies two susceptibility loci for osteosarcoma

Sharon A. Savage, Lisa Mirabello, Zhaoming Wang, Julie M. Gastier-Foster, Richard Gorlick, Chand Khanna, Adrienne M. Flanagan, Roberto Tirabosco, Irene L. Andrulis, Jay S. Wunder, Nalan Gokgoz, Ana Patiño-Garcia, Luis Sierrasesúmaga, Fernando Lecanda, Nilgün Kurucu, Inci Ergurhan Ilhan, Neriman Sari, Massimo Serra, Claudia Hattinger, Piero PicciLogan G. Spector, Donald A. Barkauskas, Neyssa Marina, Silvia Regina Caminada De Toledo, Antonio S. Petrilli, Maria Fernanda Amary, Dina Halai, David M. Thomas, Chester Douglass, Paul S. Meltzer, Kevin Jacobs, Charles C. Chung, Sonja I. Berndt, Mark P. Purdue, Neil E. Caporaso, Margaret Tucker, Nathaniel Rothman, Maria Teresa Landi, Debra T. Silverman, Peter Kraft, David J. Hunter, Nuria Malats, Manolis Kogevinas, Sholom Wacholder, Rebecca Troisi, Lee Helman, Joseph F. Fraumeni, Meredith Yeager, Robert N. Hoover, Stephen J. Chanock

Pediatrics

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

169 Scopus citations

Abstract

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10 -9) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10 -8 and 2.9 × 10 -7, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

Original language	English (US)
Pages (from-to)	799-803
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	7
DOIs	https://doi.org/10.1038/ng.2645
State	Published - Jul 2013

ASJC Scopus subject areas

Genetics

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.2645

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Savage, S. A., Mirabello, L., Wang, Z., Gastier-Foster, J. M., Gorlick, R., Khanna, C., Flanagan, A. M., Tirabosco, R., Andrulis, I. L., Wunder, J. S., Gokgoz, N., Patiño-Garcia, A., Sierrasesúmaga, L., Lecanda, F., Kurucu, N., Ilhan, I. E., Sari, N., Serra, M., Hattinger, C., ... Chanock, S. J. (2013). Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nature Genetics, 45(7), 799-803. https://doi.org/10.1038/ng.2645

Savage, SA, Mirabello, L, Wang, Z, Gastier-Foster, JM, Gorlick, R, Khanna, C, Flanagan, AM, Tirabosco, R, Andrulis, IL, Wunder, JS, Gokgoz, N, Patiño-Garcia, A, Sierrasesúmaga, L, Lecanda, F, Kurucu, N, Ilhan, IE, Sari, N, Serra, M, Hattinger, C, Picci, P, Spector, LG, Barkauskas, DA, Marina, N, De Toledo, SRC, Petrilli, AS, Amary, MF, Halai, D, Thomas, DM, Douglass, C, Meltzer, PS, Jacobs, K, Chung, CC, Berndt, SI, Purdue, MP, Caporaso, NE, Tucker, M, Rothman, N, Landi, MT, Silverman, DT, Kraft, P, Hunter, DJ, Malats, N, Kogevinas, M, Wacholder, S, Troisi, R, Helman, L, Fraumeni, JF, Yeager, M, Hoover, RN & Chanock, SJ 2013, 'Genome-wide association study identifies two susceptibility loci for osteosarcoma', Nature Genetics, vol. 45, no. 7, pp. 799-803. https://doi.org/10.1038/ng.2645

@article{3ef2f233b88c42feb2afec190c2b1d4d,

title = "Genome-wide association study identifies two susceptibility loci for osteosarcoma",

abstract = "Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10 -9) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10 -8 and 2.9 × 10 -7, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.",

author = "Savage, {Sharon A.} and Lisa Mirabello and Zhaoming Wang and Gastier-Foster, {Julie M.} and Richard Gorlick and Chand Khanna and Flanagan, {Adrienne M.} and Roberto Tirabosco and Andrulis, {Irene L.} and Wunder, {Jay S.} and Nalan Gokgoz and Ana Pati{\~n}o-Garcia and Luis Sierrases{\'u}maga and Fernando Lecanda and Nilg{\"u}n Kurucu and Ilhan, {Inci Ergurhan} and Neriman Sari and Massimo Serra and Claudia Hattinger and Piero Picci and Spector, {Logan G.} and Barkauskas, {Donald A.} and Neyssa Marina and {De Toledo}, {Silvia Regina Caminada} and Petrilli, {Antonio S.} and Amary, {Maria Fernanda} and Dina Halai and Thomas, {David M.} and Chester Douglass and Meltzer, {Paul S.} and Kevin Jacobs and Chung, {Charles C.} and Berndt, {Sonja I.} and Purdue, {Mark P.} and Caporaso, {Neil E.} and Margaret Tucker and Nathaniel Rothman and Landi, {Maria Teresa} and Silverman, {Debra T.} and Peter Kraft and Hunter, {David J.} and Nuria Malats and Manolis Kogevinas and Sholom Wacholder and Rebecca Troisi and Lee Helman and Fraumeni, {Joseph F.} and Meredith Yeager and Hoover, {Robert N.} and Chanock, {Stephen J.}",

note = "Funding Information: We thank G. Maganoli for tissue banking, M. Fanelli for DNA isolation and C. Ferrari for updating clinicopathological data at the Orthopaedic Rizzoli Institute. We thank A. Griffin and D. Marsilio for data collection and T. Selander and the Biospecimen Repository staff at Mount Sinai Hospital. We acknowledge the advice of F. Real at the Spanish National Cancer Research Centre (CNIO). We thank F. Tesser Gamba at the Pediatric Oncology Institute at GRAACC-UNIFESP, and we also thank the International Sarcoma Kindred Study. This study was funded by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health and the Bone Cancer Research Trust UK. Research is supported by the Chair{\textquoteright}s Grant U10 CA98543 and Human Specimen Banking Grant U24 CA114766 to the Children{\textquoteright}s Oncology Group from the National Cancer Institute, US National Institutes of Health. Additional support for research is provided by a grant from the WWWW (QuadW) Foundation to the Children{\textquoteright}s Oncology Group. This work was supported by grants to I.L.A. and J.S.W. from the Ontario Research Fund and Canadian Foundation for Innovation. This study was also supported by biobank grants from the Regione Emilia-Romagna and by the infrastructure and personnel of the Royal National Orthopaedic Hospital Musculoskeletal Research Programme and Biobank. Support was also provided to A.M.F. by the National Institute for Health Research UCL Hospitals (UCLH) Biomedical Research Centre and the UCL Experimental Cancer Centre. Funding was also provided by PI10/01580, the Fondo de Investigaci{\'o}n Sanitaria (FIS), the Instituto de Salud Carlos III (ISCIII) and the Caja de Ahorros de Navarra (CAN) Programme {\textquoteleft}T{\'u} eliges, t{\'u} decides{\textquoteright} to A.P.-G. and L.S. and by an Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer (AECC) project to F.L.",

year = "2013",

month = jul,

doi = "10.1038/ng.2645",

language = "English (US)",

volume = "45",

pages = "799--803",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "7",

}

TY - JOUR

T1 - Genome-wide association study identifies two susceptibility loci for osteosarcoma

AU - Savage, Sharon A.

AU - Mirabello, Lisa

AU - Wang, Zhaoming

AU - Gastier-Foster, Julie M.

AU - Gorlick, Richard

AU - Khanna, Chand

AU - Flanagan, Adrienne M.

AU - Tirabosco, Roberto

AU - Andrulis, Irene L.

AU - Wunder, Jay S.

AU - Gokgoz, Nalan

AU - Patiño-Garcia, Ana

AU - Sierrasesúmaga, Luis

AU - Lecanda, Fernando

AU - Kurucu, Nilgün

AU - Ilhan, Inci Ergurhan

AU - Sari, Neriman

AU - Serra, Massimo

AU - Hattinger, Claudia

AU - Picci, Piero

AU - Spector, Logan G.

AU - Barkauskas, Donald A.

AU - Marina, Neyssa

AU - De Toledo, Silvia Regina Caminada

AU - Petrilli, Antonio S.

AU - Amary, Maria Fernanda

AU - Halai, Dina

AU - Thomas, David M.

AU - Douglass, Chester

AU - Meltzer, Paul S.

AU - Jacobs, Kevin

AU - Chung, Charles C.

AU - Berndt, Sonja I.

AU - Purdue, Mark P.

AU - Caporaso, Neil E.

AU - Tucker, Margaret

AU - Rothman, Nathaniel

AU - Landi, Maria Teresa

AU - Silverman, Debra T.

AU - Kraft, Peter

AU - Hunter, David J.

AU - Malats, Nuria

AU - Kogevinas, Manolis

AU - Wacholder, Sholom

AU - Troisi, Rebecca

AU - Helman, Lee

AU - Fraumeni, Joseph F.

AU - Yeager, Meredith

AU - Hoover, Robert N.

AU - Chanock, Stephen J.

N1 - Funding Information: We thank G. Maganoli for tissue banking, M. Fanelli for DNA isolation and C. Ferrari for updating clinicopathological data at the Orthopaedic Rizzoli Institute. We thank A. Griffin and D. Marsilio for data collection and T. Selander and the Biospecimen Repository staff at Mount Sinai Hospital. We acknowledge the advice of F. Real at the Spanish National Cancer Research Centre (CNIO). We thank F. Tesser Gamba at the Pediatric Oncology Institute at GRAACC-UNIFESP, and we also thank the International Sarcoma Kindred Study. This study was funded by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health and the Bone Cancer Research Trust UK. Research is supported by the Chair’s Grant U10 CA98543 and Human Specimen Banking Grant U24 CA114766 to the Children’s Oncology Group from the National Cancer Institute, US National Institutes of Health. Additional support for research is provided by a grant from the WWWW (QuadW) Foundation to the Children’s Oncology Group. This work was supported by grants to I.L.A. and J.S.W. from the Ontario Research Fund and Canadian Foundation for Innovation. This study was also supported by biobank grants from the Regione Emilia-Romagna and by the infrastructure and personnel of the Royal National Orthopaedic Hospital Musculoskeletal Research Programme and Biobank. Support was also provided to A.M.F. by the National Institute for Health Research UCL Hospitals (UCLH) Biomedical Research Centre and the UCL Experimental Cancer Centre. Funding was also provided by PI10/01580, the Fondo de Investigación Sanitaria (FIS), the Instituto de Salud Carlos III (ISCIII) and the Caja de Ahorros de Navarra (CAN) Programme ‘Tú eliges, tú decides’ to A.P.-G. and L.S. and by an Asociación Española Contra el Cáncer (AECC) project to F.L.

PY - 2013/7

Y1 - 2013/7

N2 - Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10 -9) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10 -8 and 2.9 × 10 -7, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

AB - Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10 -9) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10 -8 and 2.9 × 10 -7, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

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JO - Nature Genetics

JF - Nature Genetics

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ER -

Genome-wide association study identifies two susceptibility loci for osteosarcoma

Abstract

ASJC Scopus subject areas

UN SDGs

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