Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast

Nat Commun. 2022 Jan 10;13(1):111. doi: 10.1038/s41467-021-27794-4.

Abstract

Invasive micropapillary carcinoma (IMPC) has very high rates of lymphovascular invasion and lymph node metastasis and has been reported in several organs. However, the genomic mechanisms underlying its metastasis are unclear. Here, we perform whole-genome sequencing of tumor cell clusters from primary IMPC and paired axillary lymph node metastases. Cell clusters in multiple lymph node foci arise from a single subclone of the primary tumor. We find evidence that the monoclonal metastatic ancestor in primary IMPC shares high frequency copy-number loss of PRDM16 and IGSF9 and the copy number gain of ALDH2. Immunohistochemistry analysis further shows that low expression of IGSF9 and PRDM16 and high expression of ALDH2 are associated with lymph node metastasis and poor survival of patients with IMPC. We expect these genomic and evolutionary profiles to contribute to the accurate diagnosis of IMPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / mortality
  • Carcinoma, Papillary / pathology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Evolution, Molecular
  • Female
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism
  • Lymphatic Metastasis / genetics*
  • Multigene Family
  • Neoplasm Invasiveness
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Signal Transduction
  • Survival Analysis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • IGSF9 protein, human
  • Immunoglobulins
  • Nerve Tissue Proteins
  • PRDM16 protein, human
  • Transcription Factors
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial