Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity

Rafael Guerrero-Preston, Tal Hadar, Kimberly Ostrow, Ethan Soudry, Miguel Echenique, Carmen Ili-Gangas, Gabriela Pérez, Jimena Perez, Priscilla Brebi-Mieville, José Deschamps, Luisa Morales, Manuel Bayona, David Sidransky, Jaime Matta

Research output: Contribution to journalArticle

Abstract

Methylation alterations of CpG islands, CpG island shores and first exons are key events in the formation and progression of human cancer, and an increasing number of differentially methylated regions and genes have been identified in breast cancer. Recent studies of the breast cancer methylome using deep sequencing and microarray platforms are providing a novel insight on the different roles aberrant methylation plays in molecular subtypes of breast cancer. Accumulating evidence from a subset of studies suggests that promoter methylation of tumor-suppressor genes associated with breast cancer can be quantified in circulating DNA. However, there is a paucity of studies that examine the combined presence of genetic and epigenetic alterations associated with breast cancer using blood-based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor for breast cancer that has been measured in lymphocytes. We isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL. Methylation of at least one gene was found in 49% of the cases compared to 20% of the controls. Three of the four genes had receiver characteristic operator curve values of ≥0.50: MAL(0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promotermethylation was associated with breast cancer and inverselyassociated with DRC. This is the first evidence of a significantassociation between genetic and epigenetic alterations in breastcancer using blood-based tests. The potential diagnostic utilityof these biomarkers and their relevance for breast cancer risk prediction should be examined in larger cohorts.

Original languageEnglish (US)
Pages (from-to)505-512
Number of pages8
JournalOncology Reports
Volume32
Issue number2
DOIs
StatePublished - 2014

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Keywords

  • Breast cancer
  • DNA repair capacity
  • Epigenetic biomarker panel
  • Epigenetics
  • FKBP4
  • KIF1A
  • MAL promoter methylation
  • OGDHL
  • VGF

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Guerrero-Preston, R., Hadar, T., Ostrow, K., Soudry, E., Echenique, M., Ili-Gangas, C., Pérez, G., Perez, J., Brebi-Mieville, P., Deschamps, J., Morales, L., Bayona, M., Sidransky, D., & Matta, J. (2014). Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity. Oncology Reports, 32(2), 505-512. https://doi.org/10.3892/or.2014.3262