Publication Date:
2011-08-20
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374335/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374335/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- CA097257/CA/NCI NIH HHS/ -- R01 CA133662/CA/NCI NIH HHS/ -- R01 CA138212/CA/NCI NIH HHS/ -- R01 CA169345/CA/NCI NIH HHS/ -- R01CA115699/CA/NCI NIH HHS/ -- R21CA143282/CA/NCI NIH HHS/ -- Z01 HG200337-01/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 19;333(6045):1039-43. doi: 10.1126/science.1203619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21852505" target="_blank"〉PubMed〈/a〉
Keywords:
*Aneuploidy
;
Antigens, Nuclear/*genetics/*physiology
;
Cell Cycle
;
Cell Line
;
Cell Line, Tumor
;
Chromatids/physiology
;
*Chromosomal Instability
;
Chromosomes, Human, X/genetics
;
Female
;
Gene Deletion
;
Gene Expression Profiling
;
Gene Expression Regulation, Neoplastic
;
Gene Silencing
;
Gene Targeting
;
Glioblastoma/*genetics
;
Humans
;
Karyotyping
;
Male
;
Melanoma/genetics
;
Mutation
;
Neoplasms/*genetics
;
Polymorphism, Single Nucleotide
;
Sarcoma, Ewing/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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