TMPRSS2-ERG fusions unexpectedly identified in men initially diagnosed with nonprostatic malignancies

Primo N. Lara, Andreas M. Heilmann, Julia A. Elvin, Mamta Parikh, Ralph de Vere White, Regina Gandour-Edwards, Christopher P. Evans, Chong Xian Pan, Alexa B. Schrock, Rachel Erlich, Jeffrey S. Ross, Philip J. Stephens, John McPherson, Vincent A. Miller, Siraj M. Ali

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Purpose TMPRSS2-ERG gene fusions are frequently found in prostate cancer and are pathognomonic for prostatic origin. In a series of cancer cases assayed with comprehensive genomicprofiling( CGP) inthecourseof clinicalcare,wereviewedthefrequencyofTMPRSS2-ERG fusions in patient tumors of various histologic subtypes. Methods Frequency of TMPRSS2-ERG fusions was determined in CGPs from 64,263 cancer cases submitted to Foundation Medicine to assess genomic alterations suggesting benefit from targeted therapy. Genomic results are presented from an index case of prostate cancer that underwent evolution from adenocarcinoma to pure squamous cell carcinoma. Results TMPRSS2-ERG fusions were identified for 0.86% of male patients (250 of 29,030) and not found for female patients (none of 35,233). TMPRSS2-ERG fusions were detected in six tumors classified as squamous carcinoma, five of which were of unknown primary site. Theindex case is a patient with a large, left retrovesical mass diagnosed as squamous carcinoma by morphologic examination and a history of Gleason score 9 prostate cancer with prior prostatectomy and salvage radiation therapy. TMPRSS2-ERG was detected by genomic profiling in the squamous cell tumor, the primary adenocarcinoma of the prostate, and in a metachronous prostatic adenocarcinoma metastasis.Onthe basis of these results, the patient receivedandrogen deprivation therapy. A phylogenetic tree demonstrating clonal and histopathologic evolution of prostate cancer in the index patient was constructed. Conclusion In this largeCGPdataset,TMPRSS2-ERGfusion was seen in approximately30%of prostate cancers regardless of histologic type; on occasion, the fusion was detected in advanced cancers not initially carrying a diagnosis of prostate carcinoma.CGPof advanced cancers in men may reveal prostatic origin by detection of the pathognomonic TMPRSS2-ERG fusion gene.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalJCO Precision Oncology
Issue number1
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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