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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MSK Authors
  1. Marc Ladanyi
    879 Ladanyi
  2. Neerav Shukla
    72 Shukla