Chr20q Amplification Defines a Distinct Molecular Subtype of Microsatellite Stable Colorectal Cancer

Cancer Res. 2021 Apr 15;81(8):1977-1987. doi: 10.1158/0008-5472.CAN-20-4009. Epub 2021 Feb 22.


Colorectal cancer is the third leading cause of cancer-related death in the United States. About 15% of colorectal cancers are associated with microsatellite instability (MSI) due to loss of function in the DNA mismatch repair pathway. This subgroup of patients has better survival rates and is more sensitive to immunotherapy. However, it remains unclear whether microsatellite stable (MSS) patients with colorectal cancer can be further stratified into subgroups with differential clinical characteristics. In this study, we analyzed The Cancer Genome Atlas data and found that Chr20q amplification is the most frequent copy number alteration that occurs specifically in colon (46%) and rectum (61%) cancer and is mutually exclusive with MSI. Importantly, MSS patients with Chr20q amplification (MSS-A) were associated with better recurrence-free survival compared with MSS patients without Chr20q amplification (MSS-N; P = 0.03). MSS-A tumors were associated with high level of chromosome instability and low immune infiltrations. In addition, MSS-A and MSS-N tumors were associated with somatic mutations in different driver genes, with high frequencies of mutated TP53 in MSS-A and mutated KRAS and BRAF in MSS-N. Our results suggest that MSS-A and MSS-N represent two subtypes of MSS colorectal cancer, and such stratification may be used to improve therapeutic treatment in an individualized manner. SIGNIFICANCE: This study shows that chromosome 20q amplification occurs predominately in microsatellite-stable colorectal cancer and defines a distinct subtype with good prognosis, high chromosomal instability, distinct mutation profiles, and low immune infiltrations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromosomal Instability
  • Chromosomes, Human, 19-20 / genetics*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / immunology
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • DNA Copy Number Variations
  • DNA Mismatch Repair
  • Databases, Genetic
  • Gene Amplification*
  • Genes, p53 / genetics
  • Genes, ras / genetics
  • Humans
  • Microsatellite Instability
  • Microsatellite Repeats / genetics*
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / immunology


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf