Chemo brain or tumor brain - that is the question: The presence of extracranial tumors profoundly affects molecular processes in the prefrontal cortex of TumorGraft mice

Anna Kovalchuk, Yaroslav Ilnytskyy, Rocio Rodriguez-Juarez, Svitlana Shpyleva, Stepan Melnyk, Igor Pogribny, Amanda Katz, David Sidransky, Olga Kovalchuk, Bryan Kolb

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer chemotherapy causes numerous persistent central nervous system complications. This condition is known as chemo brain. Cognitive impairments occur even before treatment, and hence are referred to as cancer associated cognitive changes, or tumor brain. There is much yet to be learned about the mechanisms of both chemo brain and tumor brain. The frequency and timing of chemo brain and tumor brain occurrence and persistence strongly suggest they may be epigenetic in nature and associated with altered gene expression. Here we used TumorGraftTM models wherein part of a patient's tumor is removed and grafted into immunedeficient mice and conducted global gene expression and DNA methylation analysis. We show that malignant non-central nervous system tumor growth causes profound molecular alterations in the brain. Mice harbouring triple negative or progesterone positive breast cancer TumorGrafts exhibited altered gene expression, decreased levels of DNA methylation, increased levels of DNA hydroxymethylation, and oxidative stress in the prefrontal cortex. Interestingly, chemotherapy did not have any additional synergistic effects on the analyzed processes. The molecular changes observed in this study are known signs of neurodegeneration and brain aging. This study provides an important roadmap for future large-scale analysis of the molecular and cellular mechanisms of tumor brain.

Original languageEnglish (US)
Pages (from-to)1660-1676
Number of pages17
JournalAging
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Keywords

  • Aging
  • Chemo brain
  • DNA methylation
  • Gene expression
  • Tumor brain

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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