Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI ; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI ; The Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI.
Transl Oncol. 2013 Aug 1;6(4):405-12. doi: 10.1593/tlo.13340. Print 2013 Aug.
E26 transformation-specific (ETS) 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, representing 223 melanomas, 10 nevi, and 5 normal skin tissues. None of the melanoma cases demonstrated ETS fusions; however, 6 of 114 (5.3%) melanomas were amplified for ETV1 using a break-apart FISH probe. For the six positive cases, locus-controlled FISH probes revealed that two of six cases were amplified for the ETV1 region, whereas four cases showed copy gains of the entire chromosome 7. The remaining 26 ETS family members showed no chromosomal aberrations by FISH. Quantitative polymerase chain reaction showed an average 3.4-fold (P value = .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 overexpresses ETV1 and amplification of ETV1 may be one mechanism for achieving high gene expression.
E26 转化特异性（ETS）转录因子已知参与包括前列腺癌在内的各种恶性肿瘤中的基因异常；然而，它们在黑色素瘤发生中的作用尚未得到充分探索。我们已经在两个黑色素瘤组织微阵列上完成了对 ETS 转录因子家族的所有 27 个成员的全面荧光原位杂交（FISH）筛选，代表了 223 个黑色素瘤、10 个痣和 5 个正常皮肤组织。没有一例黑色素瘤病例显示 ETS 融合；然而，使用分离 FISH 探针，114 例黑色素瘤中有 6 例（5.3%）扩增了 ETV1。对于这 6 个阳性病例，位点控制 FISH 探针显示 6 个病例中有 2 个扩增了 ETV1 区域，而 4 个病例显示整个 7 号染色体的拷贝数增加。其余 26 个 ETS 家族成员通过 FISH 没有显示染色体异常。定量聚合酶链反应显示，与其他恶性肿瘤（前列腺癌、乳腺癌和膀胱癌）相比，黑色素瘤中 ETV1 的表达平均增加了 3.4 倍（P 值=0.00218），包括 FISH 检测到的 ETV1 扩增病例。这些数据表明，一部分黑色素瘤过度表达 ETV1，并且 ETV1 的扩增可能是实现高基因表达的一种机制。
