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Mutations in key gene linked to different forms of cancer
|Study:||Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer|
|By:||Solomon D.A. et al. (15 authors total)|
To investigate the role of the X-chromosome STAG2 gene, which is sometimes absent (deleted) from cancer cell genomes; the STAG2 protein is involved in the process of chromosomal replication.
Multiple cancer cell lines derived from a range of human tumour types were examined for STAG2 gene sequences and STAG2 protein levels. Cancer tissue samples were examined for expression of STAG2. Chromosome numbers in experimental cell lines were assessed with and without artificial STAG2 mutations.
A range of different mutations in the STAG2 gene were identified in cancer cells.STAG2 protein was present in normal cells but absent from 14% of glioblastoma, 56% of Ewing’s sarcoma and 10% of melanoma cell lines tested. STAG2 was also absent from 19% of glioblastoma, 21% of Ewing’s sarcoma and 19% of melanoma tissue samples. Cells containing STAG2 mutations showed abnormal numbers of chromosomes (aneuploidy), but correction of these mutations and restoration of STAG2 production in cell lines increased chromosome numbers towards normal levels.
Diverse human cancers contain mutations in the STAG2 gene. STAG2 may act as a ‘caretaker’ tumour suppressor gene; inactivation due to mutations results in chromosomal instability and aneuploidy.
This research reveals an interesting new ‘handle’ on cancer; a common mutation that could underlie a significant proportion of many cancers, although not necessarily all; a much lower proportion (2-5%) of some other tumour types examined had lost STAG2. Lead researcher Professor Todd Waldman said that they were now looking to see if the STAG2 gene is mutated in other common human cancers, and raised the possibility of targeting drugs to cells with defective genes (see BBC news).