Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors
Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2017
|
| _version_ | 1826297170670649344 |
|---|---|
| author | Cheng, J Demeulemeester, J Wedge, DC Vollan, HKM Pitt, JJ Russnes, HG Pandey, BP Nilsen, G Nord, S Bignell, GR White, KP Børresen-Dale, AL Campbell, PJ Kristensen, VN Stratton, MR Lingjærde, OC Moreau, Y Loo, PV |
| author_facet | Cheng, J Demeulemeester, J Wedge, DC Vollan, HKM Pitt, JJ Russnes, HG Pandey, BP Nilsen, G Nord, S Bignell, GR White, KP Børresen-Dale, AL Campbell, PJ Kristensen, VN Stratton, MR Lingjærde, OC Moreau, Y Loo, PV |
| author_sort | Cheng, J |
| collection | OXFORD |
| description | Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2, are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis. |
| first_indexed | 2024-03-07T04:27:30Z |
| format | Journal article |
| id | oxford-uuid:cd270677-82f7-49d9-ae48-b99fe0fd70e7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:27:30Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:cd270677-82f7-49d9-ae48-b99fe0fd70e72022-03-27T07:26:48ZPan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cd270677-82f7-49d9-ae48-b99fe0fd70e7EnglishSymplectic Elements at OxfordSpringer Nature2017Cheng, JDemeulemeester, JWedge, DCVollan, HKMPitt, JJRussnes, HGPandey, BPNilsen, GNord, SBignell, GRWhite, KPBørresen-Dale, ALCampbell, PJKristensen, VNStratton, MRLingjærde, OCMoreau, YLoo, PVHomozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2, are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis. |
| spellingShingle | Cheng, J Demeulemeester, J Wedge, DC Vollan, HKM Pitt, JJ Russnes, HG Pandey, BP Nilsen, G Nord, S Bignell, GR White, KP Børresen-Dale, AL Campbell, PJ Kristensen, VN Stratton, MR Lingjærde, OC Moreau, Y Loo, PV Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| title | Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| title_full | Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| title_fullStr | Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| title_full_unstemmed | Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| title_short | Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| title_sort | pan cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors |
| work_keys_str_mv | AT chengj pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT demeulemeesterj pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT wedgedc pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT vollanhkm pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT pittjj pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT russneshg pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT pandeybp pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT nilseng pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT nords pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT bignellgr pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT whitekp pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT børresendaleal pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT campbellpj pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT kristensenvn pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT strattonmr pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT lingjærdeoc pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT moreauy pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors AT loopv pancanceranalysisofhomozygousdeletionsinprimarytumoursuncoversraretumoursuppressors |