TY - JOUR
T1 - Mutational inactivation of STAG2 causes aneuploidy in human cancer
AU - Solomon, David A.
AU - Kim, Taeyeon
AU - Diaz-Martinez, Laura A.
AU - Fair, Joshlean
AU - Elkahloun, Abdel G.
AU - Harris, Brent T.
AU - Toretsky, Jeffrey A.
AU - Rosenberg, Steven A.
AU - Shukla, Neerav
AU - Ladanyi, Marc
AU - Samuels, Yardena
AU - James, C. David
AU - Yu, Hongtao
AU - Kim, Jung Sik
AU - Waldman, Todd
PY - 2011/8/19
Y1 - 2011/8/19
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1203619
DO - 10.1126/science.1203619
M3 - Article
C2 - 21852505
AN - SCOPUS:80051874823
SN - 0036-8075
VL - 333
SP - 1039
EP - 1043
JO - Science
JF - Science
IS - 6045
ER -