Genetic analysis of uterine adenosarcomas and phyllodes tumors of the breast

Mol Oncol. 2017 Aug;11(8):913-926. doi: 10.1002/1878-0261.12049. Epub 2017 May 16.

Abstract

Uterine adenosarcomas and breast phyllodes tumors (PTs) are morphologically similar, being composed of stromal projections in a leaf-like fashion lined by epithelial cells. Here, we investigated whether their histologic similarities would be mirrored at the genetic level. The previously reported repertoires of somatic genetic alterations found in 19 adenosarcomas and 22 PTs (six benign, six borderline, and 10 malignant) were compared. PTs significantly more frequently displayed mutations affecting MED12, the TERT gene promoter and bona fide cancer genes, whereas adenosarcomas harbored a higher rate of MDM2/CDK4 and TERT gene amplifications. Pathway analyses based on the genes affected by somatic genetic alterations in these tumors indicated that Wnt signaling likely plays a role in the biology of adenosarcomas and benign/borderline PTs. In conclusion, despite the differences at the gene level, PTs and adenosarcomas share remarkable morphologic similarities and enrichment for somatic genetic alterations affecting Wnt pathway-related genes.

Keywords: genotypic-phenotypic correlation; gynecology; next-generation sequencing; pan-cancer analysis; pathology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosarcoma / genetics*
  • Adenosarcoma / metabolism
  • Adenosarcoma / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Phyllodes Tumor / genetics*
  • Phyllodes Tumor / metabolism
  • Phyllodes Tumor / pathology
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology
  • Wnt Signaling Pathway*

Substances

  • Neoplasm Proteins

Supplementary concepts

  • Adenosarcoma of the uterus