Cancer Vulnerabilities Unveiled by Genomic Loss
Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy number losses, we performed integrated analyses of genome-wide copy number and RNAi profiles a...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier B.V.
2014
|
| Online Access: | http://hdl.handle.net/1721.1/91899 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1811006745000017920 |
|---|---|
| author | Nijhawan, Deepak Zack, Travis I. Ren, Yin Strickland, Matthew R. Lamothe, Rebecca Schumacher, Steven E. Tsherniak, Aviad Besche, Henrike C. Rosenbluh, Joseph Shehata, Shyemaa Cowley, Glenn S. Weir, Barbara A. Goldberg, Alfred L. Mesirov, Jill P. Root, David E. Beroukhim, Rameen Hahn, William C. Bhatia, Sangeeta N |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Nijhawan, Deepak Zack, Travis I. Ren, Yin Strickland, Matthew R. Lamothe, Rebecca Schumacher, Steven E. Tsherniak, Aviad Besche, Henrike C. Rosenbluh, Joseph Shehata, Shyemaa Cowley, Glenn S. Weir, Barbara A. Goldberg, Alfred L. Mesirov, Jill P. Root, David E. Beroukhim, Rameen Hahn, William C. Bhatia, Sangeeta N |
| author_sort | Nijhawan, Deepak |
| collection | MIT |
| description | Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy number losses, we performed integrated analyses of genome-wide copy number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cells harboring partial copy number loss of that gene. These CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes are enriched for spliceosome, proteasome, and ribosome components. One CYCLOPS gene, PSMC2, encodes an essential member of the 19S proteasome. Normal cells express excess PSMC2, which resides in a complex with PSMC1, PSMD2, and PSMD5 and acts as a reservoir protecting cells from PSMC2 suppression. Cells harboring partial PSMC2 copy number loss lack this complex and die after PSMC2 suppression. These observations define a distinct class of cancer-specific liabilities resulting from genome instability. |
| first_indexed | 2024-09-23T16:56:59Z |
| format | Article |
| id | mit-1721.1/91899 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:56:59Z |
| publishDate | 2014 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/918992022-10-03T09:19:54Z Cancer Vulnerabilities Unveiled by Genomic Loss Nijhawan, Deepak Zack, Travis I. Ren, Yin Strickland, Matthew R. Lamothe, Rebecca Schumacher, Steven E. Tsherniak, Aviad Besche, Henrike C. Rosenbluh, Joseph Shehata, Shyemaa Cowley, Glenn S. Weir, Barbara A. Goldberg, Alfred L. Mesirov, Jill P. Root, David E. Beroukhim, Rameen Hahn, William C. Bhatia, Sangeeta N Harvard University--MIT Division of Health Sciences and Technology Koch Institute for Integrative Cancer Research at MIT Bhatia, Sangeeta N. Ren, Yin Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy number losses, we performed integrated analyses of genome-wide copy number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cells harboring partial copy number loss of that gene. These CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes are enriched for spliceosome, proteasome, and ribosome components. One CYCLOPS gene, PSMC2, encodes an essential member of the 19S proteasome. Normal cells express excess PSMC2, which resides in a complex with PSMC1, PSMD2, and PSMD5 and acts as a reservoir protecting cells from PSMC2 suppression. Cells harboring partial PSMC2 copy number loss lack this complex and die after PSMC2 suppression. These observations define a distinct class of cancer-specific liabilities resulting from genome instability. National Institutes of Health (U.S.) (NIH/NCI grant RC2 CA148268) National Institutes of Health (U.S.) (NIH/NCI grant U54 CA143798) National Institutes of Health (U.S.) (NIH/NCI grant K08 CA122833) National Institutes of Health (U.S.) (NIH/NCI grant T32 GM008313) National Institutes of Health (U.S.) (NIH/NCI grant RO1 GM051923-17) National Institutes of Health (U.S.) (NIH/NCI grant U54 CA112962) H. L. Snyder Medical Foundation Howard Hughes Medical Institute (Investigator) David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund) SASS Foundation for Medical Research, Inc V Foundation for Cancer Research Conquer Cancer Foundation (Young Investigator Award) 2014-11-24T22:01:50Z 2014-11-24T22:01:50Z 2012-08 2012-07 Article http://purl.org/eprint/type/JournalArticle 00928674 http://hdl.handle.net/1721.1/91899 Nijhawan, Deepak, Travis I. Zack, Yin Ren, Matthew R. Strickland, Rebecca Lamothe, Steven E. Schumacher, Aviad Tsherniak, et al. “Cancer Vulnerabilities Unveiled by Genomic Loss.” Cell 150, no. 4 (August 2012): 842–854. © 2012 Elsevier Inc. https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1016/j.cell.2012.07.023 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Nijhawan, Deepak Zack, Travis I. Ren, Yin Strickland, Matthew R. Lamothe, Rebecca Schumacher, Steven E. Tsherniak, Aviad Besche, Henrike C. Rosenbluh, Joseph Shehata, Shyemaa Cowley, Glenn S. Weir, Barbara A. Goldberg, Alfred L. Mesirov, Jill P. Root, David E. Beroukhim, Rameen Hahn, William C. Bhatia, Sangeeta N Cancer Vulnerabilities Unveiled by Genomic Loss |
| title | Cancer Vulnerabilities Unveiled by Genomic Loss |
| title_full | Cancer Vulnerabilities Unveiled by Genomic Loss |
| title_fullStr | Cancer Vulnerabilities Unveiled by Genomic Loss |
| title_full_unstemmed | Cancer Vulnerabilities Unveiled by Genomic Loss |
| title_short | Cancer Vulnerabilities Unveiled by Genomic Loss |
| title_sort | cancer vulnerabilities unveiled by genomic loss |
| url | http://hdl.handle.net/1721.1/91899 https://orcid.org/0000-0002-1293-2097 |
| work_keys_str_mv | AT nijhawandeepak cancervulnerabilitiesunveiledbygenomicloss AT zacktravisi cancervulnerabilitiesunveiledbygenomicloss AT renyin cancervulnerabilitiesunveiledbygenomicloss AT stricklandmatthewr cancervulnerabilitiesunveiledbygenomicloss AT lamotherebecca cancervulnerabilitiesunveiledbygenomicloss AT schumacherstevene cancervulnerabilitiesunveiledbygenomicloss AT tsherniakaviad cancervulnerabilitiesunveiledbygenomicloss AT beschehenrikec cancervulnerabilitiesunveiledbygenomicloss AT rosenbluhjoseph cancervulnerabilitiesunveiledbygenomicloss AT shehatashyemaa cancervulnerabilitiesunveiledbygenomicloss AT cowleyglenns cancervulnerabilitiesunveiledbygenomicloss AT weirbarbaraa cancervulnerabilitiesunveiledbygenomicloss AT goldbergalfredl cancervulnerabilitiesunveiledbygenomicloss AT mesirovjillp cancervulnerabilitiesunveiledbygenomicloss AT rootdavide cancervulnerabilitiesunveiledbygenomicloss AT beroukhimrameen cancervulnerabilitiesunveiledbygenomicloss AT hahnwilliamc cancervulnerabilitiesunveiledbygenomicloss AT bhatiasangeetan cancervulnerabilitiesunveiledbygenomicloss |