Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA 92868, United States.
Foundation Medicine, Inc., 150 Second Street, Cambridge, MA 02141, United States.
Lung Cancer. 2015 Jun;88(3):352-4. doi: 10.1016/j.lungcan.2015.03.014. Epub 2015 Mar 21.
ROS1-rearranged non-small cell lung cancer (NSCLC) is a unique molecularly defined yet heterogeneous subset of NSCLC. To date 12 known fusion partners of ROS1 in NSCLC have been reported. While crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has been approved for the detection of ROS1-rearrange NSCLC by the US FDA. Comprehensive genomic profiling (CGP), a subtype of clinical next-generation sequencing (NGS), offers a uniquely comprehensive and convenient approach to detect the ever-increasing and "druggable" receptor-kinase rearrangements being discovered in lung cancer.
We identified a novel ROS1 fusion variant (TMEM106B-ROS1) in a stage IV adenocarcinoma of the lung never-smoker female patient during routine genomic profiling (FoundationOne). This novel TMEM106B-ROS1 fusion variant is generated by the fusion of exons 1-3 of TMEMB106B on chromosome 7p21 to the exons 35-43 of ROS1 on chromosome 6q22. The predicted TMEM106-ROS1 protein product contains 540 amino acids comprising of the N-terminal amino acids 1-73 of TMEMB106 and C-terminal amino acids of 1881-2341 of ROS1. Although there is no predicted "coiled-coil" domain in the N-terminal domain of TMEM106B, the N-terminal domain of TMEM106B is involved in homo- and hetero-dimerization with other TMEM106 family members.
TMEM106B-ROS1 is a novel ROS1 fusion variant in NSCLC identified by comprehensive genomic profiling and should be included in any ROS1 detecting assay that depends on identifying the corresponding fusion partners such as reverse transcriptase-polymerase chain reaction (RT-PCR).
ROS1 重排非小细胞肺癌（NSCLC）是一种独特的分子定义但具有异质性的 NSCLC 亚组。迄今为止，已报道了 NSCLC 中 12 种已知的 ROS1 融合伙伴。虽然克唑替尼，一种多靶点 ALK/ROS1/MET 酪氨酸激酶抑制剂（TKI），在 ROS1 重排 NSCLC 中显示出显著的临床活性，但美国 FDA 尚未批准用于检测 ROS1 重排 NSCLC 的伴随诊断检测。综合基因组分析（CGP），一种临床下一代测序（NGS）的亚型，为检测在肺癌中发现的不断增加和“可用药”受体激酶重排提供了一种独特的全面和便捷的方法。
我们在一名从未吸烟的 IV 期肺腺癌女性患者的常规基因组分析（FoundationOne）中鉴定了一种新型 ROS1 融合变体（TMEM106B-ROS1）。这种新型 TMEM106B-ROS1 融合变体是由染色体 7p21 上的 TMEMB106B 的外显子 1-3 与染色体 6q22 上的 ROS1 的外显子 35-43 融合生成的。预测的 TMEM106-ROS1 蛋白产物包含 540 个氨基酸，包含 TMEMB106 的 N 端氨基酸 1-73 和 ROS1 的 C 端氨基酸 1881-2341。虽然 TMEM106B 的 N 端结构域中没有预测的“卷曲螺旋”结构域，但 TMEM106B 的 N 端结构域参与与其他 TMEM106 家族成员的同型和异型二聚化。
TMEM106B-ROS1 是通过综合基因组分析鉴定的 NSCLC 中的一种新型 ROS1 融合变体，应包含在任何依赖于识别相应融合伙伴的 ROS1 检测检测中，例如逆转录聚合酶链反应（RT-PCR）。
