Title |
The genetic landscape of high-risk neuroblastoma
|
---|---|
Published in |
Nature Genetics, January 2013
|
DOI | 10.1038/ng.2529 |
Pubmed ID | |
Authors |
Trevor J Pugh, Olena Morozova, Edward F Attiyeh, Shahab Asgharzadeh, Jun S Wei, Daniel Auclair, Scott L Carter, Kristian Cibulskis, Megan Hanna, Adam Kiezun, Jaegil Kim, Michael S Lawrence, Lee Lichenstein, Aaron McKenna, Chandra Sekhar Pedamallu, Alex H Ramos, Erica Shefler, Andrey Sivachenko, Carrie Sougnez, Chip Stewart, Adrian Ally, Inanc Birol, Readman Chiu, Richard D Corbett, Martin Hirst, Shaun D Jackman, Baljit Kamoh, Alireza Hadj Khodabakshi, Martin Krzywinski, Allan Lo, Richard A Moore, Karen L Mungall, Jenny Qian, Angela Tam, Nina Thiessen, Yongjun Zhao, Kristina A Cole, Maura Diamond, Sharon J Diskin, Yael P Mosse, Andrew C Wood, Lingyun Ji, Richard Sposto, Thomas Badgett, Wendy B London, Yvonne Moyer, Julie M Gastier-Foster, Malcolm A Smith, Jaime M Guidry Auvil, Daniela S Gerhard, Michael D Hogarty, Steven J M Jones, Eric S Lander, Stacey B Gabriel, Gad Getz, Robert C Seeger, Javed Khan, Marco A Marra, Matthew Meyerson, John M Maris |
Abstract |
Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 27% |
United Kingdom | 3 | 20% |
Germany | 2 | 13% |
Canada | 1 | 7% |
Italy | 1 | 7% |
Unknown | 4 | 27% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 8 | 53% |
Members of the public | 6 | 40% |
Science communicators (journalists, bloggers, editors) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 9 | 1% |
Japan | 3 | <1% |
Italy | 2 | <1% |
Spain | 2 | <1% |
United Kingdom | 1 | <1% |
China | 1 | <1% |
Canada | 1 | <1% |
Belgium | 1 | <1% |
Czechia | 1 | <1% |
Other | 0 | 0% |
Unknown | 755 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 165 | 21% |
Researcher | 162 | 21% |
Student > Master | 79 | 10% |
Student > Bachelor | 69 | 9% |
Other | 38 | 5% |
Other | 120 | 15% |
Unknown | 143 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 203 | 26% |
Agricultural and Biological Sciences | 189 | 24% |
Medicine and Dentistry | 131 | 17% |
Computer Science | 18 | 2% |
Neuroscience | 17 | 2% |
Other | 58 | 7% |
Unknown | 160 | 21% |