Whole genome profiling of rare pediatric thoracic tumors elucidates a YAP1::LEUTX fusion in an unclassified biphasic embryonal neoplasm

Pathol Res Pract. 2024 Dec:264:155726. doi: 10.1016/j.prp.2024.155726. Epub 2024 Nov 19.

Abstract

Malignant biphasic tumors of the lungs are rare, more so in the pediatric population. Here, we present the whole-genome characterization of a pleuropulmonary blastoma Type III and an unclassified biphasic thoracic embryonal neoplasm. The pleuropulmonary blastoma harbored pathogenic DICER1 germline and somatic mutations, and additional somatic variants in TP53 and BCOR. The other malignant tumor demonstrated a t(11;19) balanced translocation with a YAP1::LEUTX fusion that was confirmed by fluorescence in situ hybridization. No DICER1 germline or somatic mutation was present. YAP1 and LEUTX have been implicated in tumorigenesis of various neoplasms, and YAP1 fusion genes are an emerging oncogenic entity in a variety of malignancies. In this study we highlight the importance of whole-genome characterization of rare and unclassified tumors to identify biologic mechanisms and potential therapeutic targets.

Keywords: Novel fusion; Pleuropulmonary blastoma; Sequencing; Unclassified biphasic thoracic tumor; Whole genome; YAP1.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Child
  • DEAD-box RNA Helicases
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Oncogene Proteins, Fusion / genetics
  • Pulmonary Blastoma / genetics
  • Pulmonary Blastoma / pathology
  • Ribonuclease III
  • Transcription Factors / genetics
  • YAP-Signaling Proteins* / genetics

Substances

  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Transcription Factors
  • Adaptor Proteins, Signal Transducing
  • Oncogene Proteins, Fusion
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Supplementary concepts

  • Pleuropulmonary blastoma