Prognostic Significance of the MAD1L1 1673 G:A Polymorphism in Ovarian Adenocarcinomas

Abstract

Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism. (REV INVEST CLIN. [AHEAD OF PRINT]

Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer

“…To investigate whether RAE1 could be a therapeutic target, we performed a comprehensive analysis of 276 genes encoding microtubule‐regulating proteins 19 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 using TCGA data and evaluated their potential efficacy as a therapeutic target. We calculated the fold change in mRNA expression of each gene in tumor tissues compared to normal tissues, the correlation between mRNA expression and DNA copy number, and whether the high expression group was associated with poor prognosis.…”

Maternal genetic polymorphisms in the major mitotic checkpoint genes MAD1L1 and MAD2L1 associated with the risk of survival in abnormal chromosomal fetuses

“…In mitosis, the cell cycle arrest was impaired when MAD1 expression was downregulated by treatment with microtubule stabilizing and microtubule destabilizing agents ( Kienitz et al, 2005 ). Mutation frequencies of the SAC genes remained low, and only rare polymorphisms in MAD1L1 , MAD2L1 , and BUB1b were found in certain cancers involved in the modulation of the cell cycle arrest ( Su et al, 2016 ; Bandala-Jacques et al, 2020 ; Sun et al, 2020 ).…”

“…We then found a significant difference in the frequency for MAD1L 1 rs1801368 C>T between cases and controls. In some studies, the polymorphism in the MAD1L1 rs1801368 T allele has been found to be associated with certain kinds of cancer that showed somatic cell aneuploidy ( Santibanez et al, 2013 ; Zhong et al, 2015 ; Bandala-Jacques et al, 2020 ). However, interestingly, our result of MAD1L1 rs1801368 C>T was contrary to those reports.…”