Responsiveness to PD-1 Blockade in End-Stage Colon Cancer with Gene Locus 9p24.1 Copy-Number Gain

Cancer Immunol Res. 2019 May;7(5):701-706. doi: 10.1158/2326-6066.CIR-18-0777. Epub 2019 Feb 25.


Most patients whose large bowel cancer has spread to other organs do not respond to immune therapy. We detected a rare gene mutation, termed 9p24.1 copy-number gain (CNG), in an otherwise incurable colorectal cancer that provoked an immune therapy response. We identified this gene mutation by gene-panel sequencing of DNA from a liver metastasis biopsy from a patient who had disease refractory to standard therapies. Following immune checkpoint blockade (ICB) with pembrolizumab (anti-PD-1), the patient experienced conversion of the tumor phenotype from one with epithelial features to that of an inflamed microenvironment, detected by high-resolution RNA sequencing. Circulating tumor DNA disappeared over the first weeks of therapy. As assessed by standard radiographic measurement, the patient had a partial response that was durable. This patient's response may support the use of histology-agnostic ICB in solid tumors that carry the rare 9p24.1 CNG.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Chromosomes, Human, Pair 9 / genetics*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA Copy Number Variations
  • Female
  • Genetic Loci
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Middle Aged
  • Mutation
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab