Loss of Chromosome 8p Governs Tumor Progression and Drug Response by Altering Lipid Metabolism

Cancer Cell. 2016 May 9;29(5):751-766. doi: 10.1016/j.ccell.2016.04.003.


Large-scale heterozygous deletions are a hallmark of cancer genomes. The concomitant loss of multiple genes creates vulnerabilities that are impossible to reveal through the study of individual genes. To delineate the functional outcome of chromosome 8p loss of heterozygosity (LOH), a common aberration in breast cancer, we modeled 8p LOH using TALEN-based genomic engineering. 8p LOH alters fatty acid and ceramide metabolism. The shift in lipid metabolism triggers invasiveness and confers tumor growth under stress conditions due to increased autophagy. The resistance of 8p-deleted cells to chemotherapeutic drugs concurs with poorer survival rates of breast cancer patients harboring an 8p LOH. The autophagy dependency of 8p-deleted cells provides the rational basis for treatment of 8p LOH tumors with autophagy inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Hypoxia
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 8 / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Kaplan-Meier Estimate
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Multivariate Analysis
  • Prognosis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism


  • Antineoplastic Agents