The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Integrative genomics identifies LMO1 as a neuroblastoma oncogene
Open accessAbstract
Neuroblastoma is a childhood cancer of the sympathetic nervous system that accounts for approximately 10% of all paediatric oncology deaths. To identify genetic risk factors for neuroblastoma, we performed a genome-wide association study (GWAS) on 2,251 patients and 6,097 control subjects of European ancestry from four case series. Here we report a significant association within LIM domain only 1 (LMO1) at 11p15.4 (rs110419, combined P = 5.2 × 10−16, odds ratio of risk allele = 1.34 (95% confidence interval 1.25–1.44)). The signal was enriched in the subset of patients with the most aggressive form of the disease. LMO1 encodes a cysteine-rich transcriptional regulator, and its paralogues (LMO2, LMO3 and LMO4) have each been previously implicated in cancer. In parallel, we analysed genome-wide DNA copy number alterations in 701 primary tumours. We found that the LMO1 locus was aberrant in 12.4% through a duplication event, and that this event was associated with more advanced disease (P < 0.0001) and survival (P = 0.041). The germline single nucleotide polymorphism (SNP) risk alleles and somatic copy number gains were associated with increased LMO1 expression in neuroblastoma cell lines and primary tumours, consistent with a gain-of-function role in tumorigenesis. Short hairpin RNA (shRNA)-mediated depletion of LMO1 inhibited growth of neuroblastoma cells with high LMO1 expression, whereas forced expression of LMO1 in neuroblastoma cells with low LMO1 expression enhanced proliferation. These data show that common polymorphisms at the LMO1 locus are strongly associated with susceptibility to developing neuroblastoma, but also may influence the likelihood of further somatic alterations at this locus, leading to malignant progression.
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LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1
Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P., Lim, A., Osborne, C. S., Pawliuk, R., Morillon, E., et al. (2003) · Science · doi:10.1126/science.1088547 · Cited by 3,587
A gene atlas of the mouse and human protein-encoding transcriptomes
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Maris, J. M., Hogarty, M. D., Bagatell, R., & Cohn, S. L. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60983-0 · Cited by 2,032
Self-citationRecent Advances in Neuroblastoma
Maris, J. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0804577 · Cited by 1,983
Self-citationIdentification of ALK as a major familial neuroblastoma predisposition gene
Mossé, Y. P., Laudenslager, M., Longo, L., Cole, K. A., Wood, A., Attiyeh, E. F., Laquaglia, M. J., Sennett, R., Lynch, J. E., Perri, P., et al. (2008) · Nature · doi:10.1038/nature07261 · Cited by 1,407
Self-citationOncogenic mutations of ALK kinase in neuroblastoma
Chen, Y., Takita, J., Choi, Y. L., Kato, M., Ohira, M., Sanada, M., Wang, L., Soda, M., Kikuchi, A., Igarashi, T., et al. (2008) · Nature · doi:10.1038/nature07399 · Cited by 916
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma
Janoueix-Lerosey, I., Lequin, D., Brugières, L., Ribeiro, A., de Pontual, L., Combaret, V., Raynal, V., Puisieux, A., Schleiermacher, G., Pierron, G., et al. (2008) · Nature · doi:10.1038/nature07398 · Cited by 894
Activating mutations in ALK provide a therapeutic target in neuroblastoma
George, R. E., Sanda, T., Hanna, M., Fröhling, S., II, W. L., Zhang, J., Ahn, Y., Zhou, W., London, W. B., McGrady, P., et al. (2008) · Nature · doi:10.1038/nature07397 · Cited by 893
Self-citationCopy number variation at 1q21.1 associated with neuroblastoma
Diskin, S. J., Hou, C., Glessner, J. T., Attiyeh, E. F., Laudenslager, M., Bosse, K., Cole, K., Mossé, Y. P., Wood, A., Lynch, J. E., et al. (2009) · Nature · doi:10.1038/nature08035 · Cited by 354
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Qing, G., Li, B., Vu, A., Skuli, N., Walton, Z. E., Liu, X., Mayes, P. A., Wise, D. R., Thompson, C. B., Maris, J. M., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.09.021 · Cited by 375
Self-citationCancer Progress and Priorities: Childhood Cancer
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Metadata
- Authors
- Wang, K., Diskin, S. J., Zhang, H., Attiyeh, E. F., Winter, C., Hou, C., Schnepp, R. W., Diamond, M., Bosse, K., Mayes, P. A., Glessner, J., Kim, C., Frackelton, E., Garris, M., Wang, Q., Glaberson, W., Chiavacci, R., Nguyen, L., Jagannathan, J., Saeki, N., Sasaki, H., Grant, S. F. A., Iolascon, A., Mosse, Y. P., Cole, K. A., Li, H., Devoto, M., McGrady, P. W., London, W. B., Capasso, M., Rahman, N., Hakonarson, H., & Maris, J. M.
- Venue
- Nature
- Published
- 2010-12-01
- Volume
- 469
- Issue
- 7329
- Pages
- 216-220
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1968530152
- Cited by
- 310
- References
- 22
- FWCI
- 10.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Wang, K., Diskin, S. J., Zhang, H., Attiyeh, E. F., Winter, C., Hou, C., Schnepp, R. W., Diamond, M., Bosse, K., Mayes, P. A., Glessner, J., Kim, C., Frackelton, E., Garris, M., Wang, Q., Glaberson, W., Chiavacci, R., Nguyen, L., Jagannathan, J., . . . Maris, J. M. (2011). Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature. https://doi.org/10.1038/nature09609
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