@article{07a25d05c5894924a9a90ed79c8cca85,
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.",
author = "DA Solomon and T Kim and LA Diaz-Martinez and J Fair and AG Elkahloun and BT Harris and JA Toretsky and SA Rosenberg and N Shukla and M Ladanyi and Yardena Samuels and CD James and HT Yu and JS Kim and T Waldman",
note = "NIH [R01CA115699, R21CA143282]; SPORE grant [CA097257]; American Cancer Society [RSG0619101]; National Human Genome Research Institute, NIH We thank K. Creswell, S. Sen, and Applied Genetics Laboratories for technical assistance; and M. White and the Brain Tumor Tissue Bank of Canada, S. Baker, F. Bunz, J.-M. Peters, and the Children's Oncology Group for reagents and tumor samples. This research was supported by NIH grants R01CA115699 (T. W.), R21CA143282 (T. W.), SPORE grant CA097257 (C.D.J.), and American Cancer Society grant RSG0619101 (T. W.). Georgetown University has filed a patent application relating to the application of the mutations described in this work to the diagnosis and treatment of cancer. Y.S. is supported by the Intramural Research Programs of the National Human Genome Research Institute, NIH. Primer sequences are in table S6. For copy number arrays: the scanned array images and processed data sets have been deposited in the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo, dataset GSE13021). For expression microarrays: the scanned array images and processed data sets have been deposited in the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo, dataset GSE28214)",
year = "2011",
month = aug,
day = "19",
doi = "10.1126/science.1203619",
language = "الإنجليزيّة",
volume = "333",
pages = "1039--1043",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6045",
}