STK11 loss drives rapid progression in a breast cancer patient resulting in pulmonary tumor thrombotic microangiopathy

Breast Cancer. 2021 May;28(3):765-771. doi: 10.1007/s12282-020-01200-1. Epub 2021 Jan 2.

Abstract

We experienced a case of breast cancer in which liver metastases spread rapidly and the patient died of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a fatal cancer-associated respiratory complication disease. To reveal genetic alterations of the clinical course, we performed next generation sequencing of the serial specimens using the Ion AmpliSeqTM Comprehensive Cancer Panel and RNA sequencing for transcriptomic data, followed by gene set analysis. The analysis revealed an oncogenic TP53 R213* mutation in all specimens and STK11 loss in tissues sampled after disease progression. Immunohistochemistry with an anti-STK11 antibody confirmed no STK11 expression in the samples after progression. Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss. STK11 loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis.

Keywords: Breast cancer; LKB1; Next generation sequencing; Pulmonary tumour thrombotic microangiopathy; STK11.

Publication types

  • Case Reports

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / secondary*
  • Fatal Outcome
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Liver Neoplasms / complications
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Middle Aged
  • Mutation
  • Protein Serine-Threonine Kinases
  • Thrombotic Microangiopathies / etiology*

Substances

  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases