Publication in Translational Oncology

Comprehensive analysis of ETS family members in melanoma by fluorescence in situ hybridization reveals recurrent ETV1 amplification

Rohit Mehra, Saravana M Dhanasekaran, Nallasivam Palanisamy, Pankaj Vats, Xuhong Cao, Jung H Kim, David SL Kim, Timothy Johnson, Douglas R Fullen and Arul M Chinnaiyan

Year 2013, Volume 6, Issue 4

Abstract

ETS (E26 transformation-specific) transcription factors are known to be involved in gene aberrations in various malignancies including prostate cancer, however, their role in melanoma oncogenesis has yet to be fully explored. We have completed a comprehensive fluorescence in situ hybridization (FISH) based screen for all 27 members of the ETS transcription factor family on two melanoma tissue microarrays (TMAs), representing 223 melanomas, 10 nevi, and 5 normal skin tissues. None of the melanoma cases demonstrated ETS fusions; however, 6/114 (5.3%) melanomas were amplified for ETV1 using a break-apart FISH probe. For the 6 positive cases, locus-controlled FISH probes revealed that 2/6 cases were amplified for the ETV1 region whereas 4 cases showed copy gains of entire chromosome 7. The remaining 26 ETS family members showed no chromosomal aberrations by FISH. Q-PCR showed an average 3.4-fold (p-value 0.00218) increased expression of ETV1 in melanomas, including the FISH ETV1 amplified cases, when compared to other malignancies (prostate, breast, and bladder carcinomas). These data suggest that a subset of melanomas over-express ETV1 and amplification of ETV1 may be one mechanism for achieving high gene expression.