Comprehensive genomic profiling of malignant phyllodes tumors of the breast

Sahar Nozad, Christine E. Sheehan, Laurie M. Gay, Julia A. Elvin, Jo Anne Vergilio, James Suh, Shakti Ramkissoon, Alexa B. Schrock, Kim M. Hirshfield, Nadia Ali, Shridar Ganesan, Siraj M. Ali, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross, Jon H. Chung

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Purpose: Malignant phyllodes tumors (MPT) are exceptionally rare, and the genomic drivers of these tumors are still being elucidated. We performed comprehensive genomic profiling (CGP) of MPT to identify genomic alterations that will inform approaches to targeted therapy for patients with MPT, including relapsed, refractory, and metastatic disease. Methods: DNA was extracted from formalin-fixed, paraffin-embedded samples from 24 consecutive patient cases of MPT. CGP was performed using a hybrid capture, adaptor ligation-based next generation sequencing assay to a high, uniform coverage (mean, 582×). Tumor mutational burden (TMB) was calculated from a minimum of 1.14 Mb of sequenced DNA as previously described and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations, including short variants (SV; base substitutions, small insertions, and deletions), rearrangements, and copy number changes, including amplifications and homozygous deletions. Results: The 24 cases of MPT included 15 patients with localized and 9 with metastatic disease. The median TMB was 2.7 mut/Mb, and no cases had a TMB > 10 mut/Mb. 20 out of 24 cases were evaluable for microsatellite status, and all were microsatellite stable. The most commonly mutated genes were TP53 (58.3%), TERT-promoter (57.9%), NF1 (45.8%), MED12 (45.8%), CDKN2A/B (33.3%), and MLL2 (33.3%). Targetable kinase fusions including KIAA1549-BRAF or FGFR3-TACC3 were identified in 2/24 (8.3%) tumors. Conclusions: This study identifies clinically relevant genomic alterations that suggest novel targeted therapy approaches for patients with MPT.

Original languageEnglish (US)
Pages (from-to)597-602
Number of pages6
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - Apr 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


  • Comprehensive genomic profiling
  • MED12
  • Malignant phyllodes tumor
  • NF1
  • Targeted therapy


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