Mutational inactivation of STAG2 causes aneuploidy in human cancer

David A. Solomon, Taeyeon Kim, Laura A. Diaz-Martinez, Joshlean Fair, Abdel G. Elkahloun, Brent T. Harris, Jeffrey A. Toretsky, Steven A. Rosenberg, Neerav Shukla, Marc Ladanyi, Yardena Samuels, C. David James, Hongtao Yu, Jung Sik Kim, Todd Waldman

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1039-1043
Number of pages5
JournalScience
Volume333
Issue number6045
DOIs
StatePublished - Aug 19 2011

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Aneuploidy
Chromatids
Neoplasms
Cell Line
X Chromosome Inactivation
Chromosomal Instability
Glioblastoma
Diploidy
Karyotype
Cell Division
Chromosomes
Alleles
Mutation
Genes
cohesins

ASJC Scopus subject areas

  • General

Cite this

Solomon, D. A., Kim, T., Diaz-Martinez, L. A., Fair, J., Elkahloun, A. G., Harris, B. T., ... Waldman, T. (2011). Mutational inactivation of STAG2 causes aneuploidy in human cancer. Science, 333(6045), 1039-1043. https://doi.org/10.1126/science.1203619

Mutational inactivation of STAG2 causes aneuploidy in human cancer. / Solomon, David A.; Kim, Taeyeon; Diaz-Martinez, Laura A.; Fair, Joshlean; Elkahloun, Abdel G.; Harris, Brent T.; Toretsky, Jeffrey A.; Rosenberg, Steven A.; Shukla, Neerav; Ladanyi, Marc; Samuels, Yardena; James, C. David; Yu, Hongtao; Kim, Jung Sik; Waldman, Todd.

In: Science, Vol. 333, No. 6045, 19.08.2011, p. 1039-1043.

Research output: Contribution to journalArticle

Solomon, DA, Kim, T, Diaz-Martinez, LA, Fair, J, Elkahloun, AG, Harris, BT, Toretsky, JA, Rosenberg, SA, Shukla, N, Ladanyi, M, Samuels, Y, James, CD, Yu, H, Kim, JS & Waldman, T 2011, 'Mutational inactivation of STAG2 causes aneuploidy in human cancer', Science, vol. 333, no. 6045, pp. 1039-1043. https://doi.org/10.1126/science.1203619
Solomon DA, Kim T, Diaz-Martinez LA, Fair J, Elkahloun AG, Harris BT et al. Mutational inactivation of STAG2 causes aneuploidy in human cancer. Science. 2011 Aug 19;333(6045):1039-1043. https://doi.org/10.1126/science.1203619
Solomon, David A. ; Kim, Taeyeon ; Diaz-Martinez, Laura A. ; Fair, Joshlean ; Elkahloun, Abdel G. ; Harris, Brent T. ; Toretsky, Jeffrey A. ; Rosenberg, Steven A. ; Shukla, Neerav ; Ladanyi, Marc ; Samuels, Yardena ; James, C. David ; Yu, Hongtao ; Kim, Jung Sik ; Waldman, Todd. / Mutational inactivation of STAG2 causes aneuploidy in human cancer. In: Science. 2011 ; Vol. 333, No. 6045. pp. 1039-1043.
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