ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non-Small Cell Lung Cancer.
ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non-Small Cell Lung Cancer.
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DOI：
10.1016/j.jtho.2017.01.004
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Shaw AT
中科院分区：
文献类型：
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作者：
Lin JJ;Ritterhouse LL;Ali SM;Bailey M;Schrock AB;Gainor JF;Ferris LA;Mino-Kenudson M;Miller VA;Iafrate AJ;Lennerz JK;Shaw AT
涉及ROS原癌基因1受体酪氨酸激酶基因（ROS 1）的染色体重排定义了对ROS 1抑制剂敏感的非小细胞肺癌（NSCLC）的一个独特分子亚群。最近的报告表明，ROS 1融合和其他致癌驱动改变之间存在显著重叠，包括表皮生长因子受体（EGFR）和KRAS原癌基因（KRAS）的突变。我们确定了在我们机构接受过其他癌基因（包括EGFR、KRAS和间变性淋巴瘤激酶（ALK））遗传学改变检测的ROS 1重排NSCLC患者。本文回顾了其临床病理特征和基因检测结果。我们还检查了通过商业FoundationOne测定鉴定的ROS 1重排NSCLC的单独数据库。在我们机构评价的62例ROS 1重排NSCLC患者中，无患者同时存在ALK融合（0%）或EGFR激活突变（0%）。在2例病例（3.2%）中检测到KRAS突变，其中1例同时存在生物学意义未知的非典型KRAS I24 N突变。在另一个ROS 1 FISH阳性病例中，靶向测序未能确认ROS 1融合，而是鉴定出KRAS G13 D突变。未检测到BRAF、ERBB 2、PIK 3CA、AKT 1或MAP 2K 1的并发突变。对FoundationOne确定的166例ROS 1重排NSCLC的独立数据集的分析表明，EGFR（1/166）和KRAS（3/166）中同时发生驱动突变的病例非常罕见，没有同时发生ROS 1和ALK重排的病例。在NSCLC中，ROS 1重排很少与EGFR、KRAS、ALK或其他靶向癌基因的改变重叠。
Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK). Clinicopathologic features and genetic testing results were reviewed. We also examined a separate database of ROS1-rearranged NSCLCs identified through a commercial FoundationOne assay. Among 62 patients with ROS1-rearranged NSCLC evaluated at our institution, none harbored concurrent ALK fusions (0%) or EGFR activating mutations (0%). KRAS mutations were detected in two cases (3.2%), one of which harbored a concurrent non-canonical KRAS I24N mutation of unknown biological significance. In a separate ROS1 FISH-positive case, targeted sequencing failed to confirm a ROS1 fusion, but instead identified a KRAS G13D mutation. No concurrent mutations in BRAF, ERBB2, PIK3CA, AKT1, or MAP2K1 were detected. Analysis of an independent dataset of 166 ROS1-rearranged NSCLCs identified by FoundationOne demonstrated rare cases with co-occurring driver mutations in EGFR (1/166) and KRAS (3/166), and no cases with co-occurring ROS1 and ALK rearrangements. ROS1 rearrangements rarely overlap with alterations in EGFR, KRAS, ALK, or other targetable oncogenes in NSCLC.