Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer

Int J Mol Sci. 2020 Feb 14;21(4):1290. doi: 10.3390/ijms21041290.

Abstract

We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in TP53 (47.3%), PMS2 (26.3%), MRE11 (26.3%), RB1 (10.5%), BRCA1 (10.5%), PTEN (10.5%) and AR (10.5%); other affected genes included PMS1, KMT2C, BRCA2, PALB2, MUTYH, MEN1, MSH2, CHEK2, NCOR1, PIK3CA, ESR1 and MAP2K4. In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AFtissue ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.

Keywords: cell-free DNA (cfDNA); inflammatory breast cancer (IBC); next generation sequencing (NGS).

MeSH terms

  • Adult
  • Aged
  • Alleles
  • BRCA2 Protein / genetics
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell-Free Nucleic Acids / chemistry
  • Cell-Free Nucleic Acids / genetics*
  • Female
  • Gene Frequency
  • Genetic Variation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / genetics
  • Neoplasm Staging
  • Tumor Suppressor Protein p53 / genetics

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • Cell-Free Nucleic Acids
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2