Copy number variation in triple negative breast cancer samples associated with lymph node metastasis

Neoplasia. 2021 Aug;23(8):743-753. doi: 10.1016/j.neo.2021.05.016. Epub 2021 Jul 2.


Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.

Keywords: Copy number variation; Invasive ductal carcinoma; Lymph node metastasis; Triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Chromosome Mapping
  • Computational Biology / methods
  • DNA Copy Number Variations*
  • DNA Methylation
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Ontology
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Molecular Sequence Annotation
  • Neoplasm Staging
  • Prognosis
  • Triple Negative Breast Neoplasms / etiology*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology*


  • Biomarkers, Tumor