FGFR3-TACC3融合在年轻、亚洲裔或从不吸烟的膀胱癌患者中的富集情况。
Enrichment of FGFR3-TACC3 Fusions in Patients With Bladder Cancer Who Are Young, Asian, or Have Never Smoked.
作者信息
Nassar Amin H, Lundgren Kevin, Pomerantz Mark, Van Allen Eliezer, Harshman Lauren, Choudhury Atish D, Preston Mark A, Steele Graeme S, Mouw Kent W, Wei Xiao X, McGregor Bradley A, Choueiri Toni K, Bellmunt Joaquim, Kwiatkowski David J, Sonpavde Guru P
机构信息
, , , and , Brigham and Women's Hospital, Harvard Medical School; and , , , , , , , , , , and , Dana-Farber Cancer Institute, Boston, MA.
出版信息
JCO Precis Oncol. 2018 May 16;2. doi: 10.1200/PO.18.00013. eCollection 2018.
PURPOSE
(fibroblast growth factor receptor 3-transforming acidic coiled coil-containing protein 3) fusions have recently been identified as driver mutations that lead to the activation of in bladder cancer and other tumor types and are associated with sensitivity to tyrosine kinase inhibitors. We examined the clinical and molecular characteristics of patients with fusions and hypothesized that they are enriched in a subset of patients with bladder cancer.
MATERIALS AND METHODS
We correlated somatic fusions with clinical and molecular features in two cohorts of patients with bladder cancer. The first cohort consisted of the muscle-invasive bladder cancer (MIBC) data set (n = 412) from The Cancer Genome Atlas. The second cohort consisted of patients with MIBC or high-grade non-MIBC at the Dana-Farber Cancer Institute that had targeted capture sequencing of a selected panel of cancer genes (n = 356). All statistical tests were two sided. The clinical response of one patient with bladder cancer to an FGFR3 inhibitor was investigated.
RESULTS
Overall, 751 patients with high-grade bladder cancer without fusions and 17 with fusions were identified in the pooled analysis of the data sets from The Cancer Genome Atlas and the Dana-Farber Cancer Institute. fusions were enriched in patients age ≤ 50 years versus age 51 to 65 years versus those older than 65 years (pooled, = .002), and were observed in four (12%) of 33 patients age ≤ 50 years in the pooled analysis. Similarly, fusions were significantly more common in Asians (13%) compared with African Americans (4%) and whites (2%; pooled, < .001), as well as in never smokers (5.6%) compared with ever smokers (1.1%; pooled, < .001). One patient with the fusion who was treated with an FGFR3 inhibitor achieved complete remission for 10 months.
CONCLUSION
Clinical testing to identify fusions should be prioritized for patients with bladder cancer who are younger, never smokers, and/or Asian.
目的
成纤维细胞生长因子受体3-转化酸性卷曲螺旋蛋白3（FGFR3-TACC3）融合最近被鉴定为驱动突变，可导致膀胱癌和其他肿瘤类型中的激活，并与对酪氨酸激酶抑制剂的敏感性相关。我们研究了FGFR3-TACC3融合患者的临床和分子特征，并假设它们在一部分膀胱癌患者中富集。
材料与方法
我们将两个膀胱癌患者队列中的体细胞FGFR3-TACC3融合与临床和分子特征进行了关联。第一个队列由来自癌症基因组图谱的肌层浸润性膀胱癌（MIBC）数据集（n = 412）组成。第二个队列由达纳-法伯癌症研究所的MIBC或高级别非MIBC患者组成，这些患者对一组选定的癌症基因进行了靶向捕获测序（n = 356）。所有统计检验均为双侧检验。研究了一名FGFR3-TACC3膀胱癌患者对FGFR3抑制剂的临床反应。
结果
总体而言，在对癌症基因组图谱和达纳-法伯癌症研究所的数据集进行汇总分析时，共鉴定出751例无FGFR3-TACC3融合的高级别膀胱癌患者和17例有FGFR3-TACC3融合的患者。FGFR3-TACC3融合在年龄≤50岁的患者中比年龄在51至65岁的患者以及年龄大于65岁的患者中更富集（汇总分析，P = 0.002），在汇总分析中，33例年龄≤50岁的患者中有4例（12%）观察到FGFR3-TACC3融合。同样，FGFR3-TACC3融合在亚洲人中（13%）比非裔美国人（4%）和白人（2%；汇总分析，P < 0.001）更常见，在从不吸烟者中（5.6%）比曾经吸烟者中（1.1%；汇总分析，P < 0.001）更常见。一名接受FGFR3抑制剂治疗的FGFR3-TACC3融合患者实现了10个月的完全缓解。
结论
对于年龄较小、从不吸烟和/或为亚洲人的膀胱癌患者，应优先进行临床检测以识别FGFR3-TACC3融合。
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