Imbalance in DNA repair machinery is associated with BRAFV600E mutation and tumor aggressiveness in papillary thyroid carcinoma

Mol Cell Endocrinol. 2018 Sep 5:472:140-148. doi: 10.1016/j.mce.2017.12.004. Epub 2017 Dec 8.

Abstract

The involvement of alterations in MLH1, an essential mismatch repair component, in BRAFV600E mutated papillary thyroid carcinoma (PTC) has been suggested to be associated with features of tumor aggressiveness. Thirty-two PTC and surrounding normal thyroid tissues were evaluated for 11 representative DNA repair genes expression. BRAFV600E mutational status assessment and clinicopathological correlations were evaluated for their gene and protein expression. BRAFV600E PTC is associated with lower levels of XPD and MLH1 gene expression. Decrease in MLH1 and XPD mRNA levels in BRAFV600E PTC (but not their protein products) are associated with predictors of poor patient outcomes. Considering the complete subset of patients, MGMT and XRCC2 genes were shown down and upregulated, respectively, in PTC tissues. Low expression of MGMT gene and weak XRCC2 protein expression were correlated with characteristics of tumor aggressiveness. These results suggest that an imbalance in DNA repair gene expression in PTC is associated with aggressive clinicopathological features and BRAFV600E mutation.

Keywords: BRAF(V600E); DNA repair; Papillary thyroid cancer; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Repair / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mutation / genetics*
  • Neoplasm Invasiveness
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*

Substances

  • RNA, Messenger
  • Proto-Oncogene Proteins B-raf