Biomarker Discovery Program, Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Urology, Mayo Clinic, Rochester, Minnesota.
Cancer Res. 2017 Nov 15;77(22):6157-6167. doi: 10.1158/0008-5472.CAN-17-0529. Epub 2017 Nov 10.
gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between and has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens. gene fusions were observed in 44% of cases, and over 90% of these fusions occurred in exons 3 or 4. fusions retaining interstitial sequences occurred more frequently in very low-risk tumors. These tumors also frequently displayed gene fusions involving alternative 5'-partners to , specifically and and other ETS family genes, which retained interstitial sequences. Lastly, tumors displaying fusions that retained interstitial genes were less likely to be associated with biochemical recurrence ( = 0.028). Our results point to more favorable clinical outcomes in patients with ETS family fusion-positive prostate cancers, which retain potential tumor-suppressor genes in the interstitial regions between and Identifying these patients at biopsy might improve patient management, particularly with regard to active surveillance. .
基因融合发生在超过 50%的前列腺癌中，但它们对临床结果的影响尚不清楚。据报道，在动物模型中， 和 之间的间质基因保留会影响肿瘤的进展。在这项研究中，我们分析了一组接受前列腺癌根治性手术治疗的男性肿瘤中 融合基因和间质基因的状态，将这些改变与生化进展相关联。通过全基因组配对测序，我们对来自低危、中危和高危前列腺癌患者的 133 例根治性前列腺切除术标本中的 ETS 家族基因融合驱动重排进行了作图和分类。在 44%的病例中观察到了 基因融合，其中超过 90%的融合发生在 外显子 3 或 4 中。保留间质序列的 融合在低危肿瘤中更为常见。这些肿瘤也经常显示涉及 替代 5'-伙伴的 基因融合，具体为 和 以及其他 ETS 家族基因，这些基因保留了间质 序列。最后，显示保留间质基因的 融合的肿瘤与生化复发的相关性较低（=0.028）。我们的结果表明，ETS 家族融合阳性前列腺癌患者的临床结果更为有利，这些肿瘤在 和 之间的间质区域保留了潜在的肿瘤抑制基因。在活检时识别这些患者可能会改善患者的管理，特别是在主动监测方面。
