Mutational inactivation of STAG2 causes aneuploidy in human cancer Journal Article
| Authors: | Solomon, D. A.; Kim, T.; Diaz-Martinez, L. A.; Fair, J.; Elkahloun, A. G.; Harris, B. T.; Toretsky, J. A.; Rosenberg, S. A.; Shukla, N.; Ladanyi, M.; Samuels, Y.; James, C. D.; Yu, H.; Kim, J. S.; Waldman, T. |
| Article Title: | Mutational inactivation of STAG2 causes aneuploidy in human cancer |
| Abstract: | Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer. |
| Keywords: | human tissue; gene mutation; gene translocation; human cell; gene deletion; mutation; polymorphism, single nucleotide; genetic analysis; neoplasm; neoplasms; cohesin; chromosome; cytology; allele; gene targeting; cell cycle; cell division; sister chromatid; melanoma; gene expression profiling; cell line; gene locus; cancer cell culture; cell line, tumor; colorectal carcinoma; ewing sarcoma; gene expression regulation, neoplastic; glioblastoma; medulloblastoma; genomics; chromosomal instability; x chromosome; chromosomes, human, x; gene inactivation; gene silencing; tumor; tumor gene; sarcoma, ewing's; karyotype; karyotyping; aneuploidy; diploidy; chromatids; antigens, nuclear; stag2 gene |
| Journal Title: | Science |
| Volume: | 333 |
| Issue: | 6045 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2011-08-19 |
| Start Page: | 1039 |
| End Page: | 1043 |
| Language: | English |
| DOI: | 10.1126/science.1203619 |
| PUBMED: | 21852505 |
| PROVIDER: | scopus |
| PMCID: | PMC3374335 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 3 October 2011" - "CODEN: SCIEA" - "Source: Scopus" |
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