• Pharmacogenet. Genomics · Apr 2013

    The MAD1 1673 G → A polymorphism alters the function of the mitotic spindle assembly checkpoint and is associated with a worse response to induction chemotherapy and sensitivity to treatment in patients with advanced epithelial ovarian cancer.

    • Miguel Santibáñez, Dolores Gallardo, Flavia Morales, Alejandro López, Diddier Prada, Julia Mendoza, Clementina Castro, David Cantú de León, Luis F Oñate, Delia Perez, Alejandro Mohar, and Luis A Herrera.
    • Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Universidad Nacional Autónoma de México, México, DF, México.
    • Pharmacogenet. Genomics. 2013 Apr 1; 23 (4): 190-9.

    BackgroundMitotic arrest deficient 1 (MAD1), a protein of the mitotic spindle assembly checkpoint (SAC), recognizes MAD2 through two leucine zippers, transporting and activating MAD2, which promotes a metaphase arrest signal. A single nucleotide polymorphism of MAD1 was found to affect the SAC function that could be involved in a poor response to therapeutic agents that alter the dynamics of microtubules.ObjectiveThe aim of this study was to examine the relationship of the polymorphism MAD1 1673 G → A (rs1801368) with the efficiency of the SAC and the generation of aneuploidies and with the therapeutic response of patients with ovarian cancer.MethodsThe polymorphism was evaluated in 144 healthy individuals and 91 patients. Mitotic arrest and the presence of errors in segregation were analyzed in cultured human lymphocytes treated with nocodazole and paclitaxel. Errors in segregation were also evaluated in 27 biopsies of patients.ResultsAllele frequencies in healthy individuals were G: 50%, A: 50%, whereas in the patients they were G: 38%, A: 62% (P<0.05). The percentage of cells with mitotic arrest was higher among GG cells (P<0.05). The frequency of micronuclei and nondisjunction events increased in AA cells (P<0.05). Tumors from polymorphic patients had a higher percentage of aneuploid cells (P<0.05). The GG patients showed a higher biochemical response, optimal cytoreduction, and sensitivity to the treatment. There were no differences in progression-free or overall survival between both groups.ConclusionThe polymorphism MAD1 1673 G → A affects SAC functionality, increasing the frequency of aneuploid cells. This polymorphism modifies the response to agents that alter the dynamics of microtubules in patients with ovarian cancer.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…