Comprehensive characterization of malignant phyllodes tumor by whole genomic and proteomic analysis: biological implications for targeted therapy opportunities

• DOI: 10.1186/1750-1172-8-112
• Publication Date: 2013-07-30T02:15:20Z
• Authors: Denis L Fontes Ja...; Anthony Conley; Vivek Subbiah
• Keywords: Comparative genomic hybridization; Targeted Therapy

Abstract Background Phyllodes tumors are uncommon breast that account for less than 0.5% of all malignancies. After metastases develop, the prognosis is poor, with very few patients living more 1 year. The biology this unusual cancer not understood and, consequently, no potential targets treatments currently available. There has been an exponential increase in number commercially available tumor profiling services. Herein, we report a case metastatic malignant phyllodes which comprehensive molecular analysis was performed by using Clinical Laboratory Improvement Amendments (CLIA)-certified labs, providing new insights into opportunities molecularly targeted therapies extremely rare disease. Methods Next-generation sequencing FoundationOne™ platform (Foundation Medicine, Cambridge, MA). Whole-genome array-based comparative genomic hybridization (array CGH) DNAarray™ (CombiMatrix Diagnostics, Irvine, CA). Immunohistochemical and morphoproteomics were at Consultative proteomics ® , University Texas, UT Health Medical School, Houston,TX (Robert E Brown Lab); Clarient Aliso Viejo, CA; Caris Life Sciences Target one, Irving, TX, USA. Results showed 3 aberrant genes: activating mutation Q61L on NRAS ; inactivating mutations Q504* K740* RB1 TP53 loss. revealed amplifications chromosome (chr.) ( CKS1B gene), chr. 8 MYC 9 CDKN2A gene) Deletions 17 ), 10 GATA3 11 FGF4 CCND1 genes), chr.22 PDGFβ ). relevant markers positive staining transducing-like enhancer split (TLE) 3; secreted protein acidic rich cysteine (SPARC) expressed 2-3+ cytoplasm cells, whereas mammalian target rapamycin (mTOR) up to 2+ nuclei cells. Conclusions We describe first time concomitant activation PI3K / Akt mTOR tumor. also found sensitivity taxane-based therapies, especially albumin-bound paclitaxel. Exploring malignancies CLIA certified labs may be reasonable strategy development treatments.