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Common polymorphic inversions at 17q21.31 and 8p23.1 associate with cancer prognosis.


ABSTRACT: BACKGROUND:Chromosomal inversions are structural genetic variants where a chromosome segment changes its orientation. While sporadic de novo inversions are known genetic risk factors for cancer susceptibility, it is unknown if common polymorphic inversions are also associated with the prognosis of common tumors, as they have been linked to other complex diseases. We studied the association of two well-characterized human inversions at 17q21.31 and 8p23.1 with the prognosis of lung, liver, breast, colorectal, and stomach cancers. RESULTS:Using data from The Cancer Genome Atlas (TCGA), we observed that inv8p23.1 was associated with overall survival in breast cancer and that inv17q21.31 was associated with overall survival in stomach cancer. In the meta-analysis of two independent studies, inv17q21.31 heterozygosity was significantly associated with colorectal disease-free survival. We found that the association was mediated by the de-methylation of cg08283464 and cg03999934, also linked to lower disease-free survival. CONCLUSIONS:Our results suggest that chromosomal inversions are important genetic factors of tumor prognosis, likely affecting changes in methylation patterns.

SUBMITTER: Ruiz-Arenas C 

PROVIDER: S-EPMC6873427 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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