Oncogenic Fusion(致癌融合)研究综述
Oncogenic Fusion 致癌融合 - In all samples of CD30-positive LPD and MF, oncogenic fusions afflicting the JAK/STAT signaling pathway were present, namely NPM1-TYK2 in patient 1 and ILF3-JAK2 in patient 2. [1] Purpose: Oncogenic fusions involving the neuregulin 1 (NRG1) gene are found in approximately 0. [2] Oncogenic fusions represent compelling druggable targets in solid tumours highlighted by the recent site agnostic FDA approval of larotrectinib for NTRK rearrangements. [3] These alterations were detected in 14 patients, three of whom had oncogenic fusions. [4] Molecular dysregulation of KAT6A has been observed in several cancers, including amplifications in breast, lung, ovarian cancer along with oncogenic fusions in AML. [5] To address this, we have developed in vitro models of oncogenic fusions, in particular, EWSR1-CREB1 and EWSR1-ATF1, in human embryonic stem (hES) cells, which are capable of multipotent differentiation, using CRISPR-Cas9 technology and HDR together with conditional fusion gene expression that allows investigation into the early steps of cellular transformation. [6] Two selective histology-agnostic tropomyosin receptor kinase (TRK) inhibitors are currently approved for malignancies with these oncogenic fusions. [7] Addition of the oncogenic fusion to the NRAS mutation also results in a higher leukemic stem cell frequency. [8] Moreover, this work has broad implications for studies of leukemogenesis applicable to a variety of oncogenic fusion-driven pediatric leukemias, providing a robust and tractable model system to characterize the molecular mechanisms of leukemogenesis and identify biomarkers for disease diagnosis and targets for therapy. [9] Lee, and colleagues showed that oncogenic fusions were more commonly associated with invasive disease, increased expression of MAPK signaling pathway genes (ERK score), and decreased expression of the sodium-iodine symporter, which was restored by RET- and NTRK-inhibitory therapy. [10] Taken together, our findings reveal that PKC gene fusions are distinct from oncogenic fusions and present a mechanism by which loss of PKC function occurs in cancer. [11] Recently, more novel mechanisms, including rare EGFR point mutations and oncogenic fusions, were reported. [12] The latter were enriched for oncogenic fusions, with 11 non-recurrent fusion transcripts, including two previously undescribed fusions, STRN-RET and TG-PBF. [13] The presence of oncogenic fusions including NTRK fusions are rare but important to identify. [14] The molecular profile of CSM may reveal EWSR1 or FUS gene rearrangement, but as we showcase, the diagnosis remains possible in the absence of this oncogenic fusion. [15] Oncogenic fusions involving NTRK1, NTRK2, and NTRK3 with various partners are diagnostic of infantile fibrosarcoma and secretory carcinoma yet also occur in lower frequencies across many types of malignancies. [16] On the other hand, a variety of ALK gene alterations, such as oncogenic fusion, activating point mutation, or wild type gene amplification, have been recently discovered as the powerful oncogene in various tumors, and these ALK mutations have also been known as the potential therapeutic targets against tumors harboring these ALK mutations. [17] Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. [18] Chromoplexy has also been described as a mechanism of resistance, where multiple closed chain rearrangements cause loss-of-function of tumor suppressor genes and gain-in-function of oncogenic fusions. [19] To the editor, Chromosomal translocations leading to oncogenic fusions are increasingly being recognized as molecular drivers of gliomas [9]. [20] Oncogenic fusions are rare in colorectal carcinomas, but may be important for prognosis and therapy. [21] In contrast to the tumor-specific gene-rearrangement-positive acute lymphoblastic leukemia (ALL) and the oncogenic fusion-gene-positive chronic myelogenous leukemia (CML) and several solid tumors, the clinical significance of MRD remains to be established in neuroblastoma. [22] The detection of oncogenic fusions can be conducted using fluorescence in situ hybridization, reverse-transcription polymerase chain reaction, immunohistochemistry, or NGS. [23] 50% (137/275) have structural alterations in their tumors with over half of these (74/137) harboring an oncogenic fusion that is the main, or only identified, driver of the cancer. [24]nan [1] nan [2] nan [3] nan [4] nan [5] nan [6] nan [7] nan [8] nan [9] nan [10] nan [11] nan [12] nan [13] nan [14] CSM 的分子谱可能揭示 EWSR1 或 FUS 基因重排，但正如我们所展示的，在没有这种致癌融合的情况下，诊断仍然是可能的。 [15] 涉及 NTRK1、NTRK2 和 NTRK3 与各种伙伴的致癌融合可诊断婴儿纤维肉瘤和分泌性癌，但在许多类型的恶性肿瘤中也以较低的频率发生。 [16] 另一方面，最近发现多种 ALK 基因改变，如致癌融合、激活点突变或野生型基因扩增，是各种肿瘤中的强癌基因，这些 ALK 突变也被称为潜在的针对携带这些 ALK 突变的肿瘤的治疗靶点。 [17] 在骨髓增殖性肿瘤中描述了 FGFR1 与各种融合伙伴的致癌融合，并且 FGFR3 的过表达和突变在多发性骨髓瘤中很常见。 [18] Chromoplexy 也被描述为一种抗性机制，其中多个闭链重排导致肿瘤抑制基因功能丧失和致癌融合功能获得。 [19] 对编辑来说，导致致癌融合的染色体易位越来越被认为是胶质瘤的分子驱动因素 [9]。 [20] 致癌融合在结直肠癌中很少见，但可能对预后和治疗很重要。 [21] 与肿瘤特异性基因重排阳性急性淋巴细胞白血病 (ALL) 和致癌融合基因阳性慢性粒细胞白血病 (CML) 和几种实体瘤相比，MRD 在神经母细胞瘤中的临床意义仍有待确定。 [22] 可以使用荧光原位杂交、逆转录聚合酶链反应、免疫组织化学或 NGS 来检测致癌融合。 [23] 50% (137/275) 的肿瘤发生结构改变，其中超过一半 (74/137) 存在致癌融合，这是癌症的主要或唯一确定的驱动因素。 [24]
protein nucleophosmin anaplastic
BACKGROUND Inhibitors for signal transducer and activator of transcription 3 (STAT3), Stattic, BP-1-102, and LLL12 significantly induce apoptosis in transformed Ba/F3 cells expressing an oncogenic fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) that induces the activation of STAT3. [1] BACKGROUND Inhibitors for signal transducer and activator of transcription 3 (STAT3), Stattic, BP-1-102, and LLL12 significantly induce apoptosis in transformed Ba/F3 cells expressing an oncogenic fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) that induces the activation of STAT3. [2] Anaplastic large cell lymphoma (ALCL) is associated with a characteristic chromosomal translocation that generates the oncogenic fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). [3]背景 信号转导和转录激活因子 3 (STAT3)、Stattic、BP-1-102 和 LLL12 的抑制剂显着诱导转化的 Ba/F3 细胞凋亡，该细胞表达一种致癌融合蛋白核磷蛋白间变性淋巴瘤激酶 (NPM-ALK)，可诱导STAT3 的激活。 [1] 背景 信号转导和转录激活因子 3 (STAT3)、Stattic、BP-1-102 和 LLL12 的抑制剂显着诱导转化的 Ba/F3 细胞凋亡，该细胞表达一种致癌融合蛋白核磷蛋白间变性淋巴瘤激酶 (NPM-ALK)，可诱导STAT3 的激活。 [2] nan [3]
non small cell
Building an effective concordance study: Plasma Next Generation Sequencing (NGS) for oncogenic fusion detection in non-small cell lung carcinoma (NSCLC) [abstract]. [1] Introduction ROS1 oncogenic fusion, which was first identified by Rikova et al, is reported to be present in 1%–2% of non-small cell lung cancers (NSCLCs) and is defined as a distinct molecular sub-group. [2]建立有效的一致性研究：用于非小细胞肺癌 (NSCLC) 中致癌融合检测的血浆下一代测序 (NGS) [摘要]。 [1] 介绍 ROS1 致癌融合是由 Rikova 等人首先发现的，据报道存在于 1%–2% 的非小细胞肺癌 (NSCLC) 中，并被定义为一个独特的分子亚组。 [2]
anaplastic lymphoma kinase
Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 ( EML4 ) gene and the anaplastic lymphoma kinase ( ALK ) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer ( NSCLC ), mostly in non-smokers with adenocarcinoma. [1]导致棘皮动物微管相关蛋白样 4 (EML4) 基因和间变性淋巴瘤激酶 (ALK) 基因融合的染色体易位已被认为是非小细胞肺癌 (NSCLC) 子集中的一种新型致癌融合。 ，主要发生在患有腺癌的非吸烟者中。 [1]
Novel Oncogenic Fusion
The development of sequencing techniques, such as RNA-Sequencing, has identified many gene rearrangements encoding novel oncogenic fusions. [1] In each case, POG analyses identified genomic drivers including novel oncogenic fusions, aberrant pathways, and putative therapeutic targets. [2] We demonstrate that RNA-seq is a powerful tool to identify clinically relevant and histology-specific recurrent mutations, novel oncogenic fusions, and translationally relevant immunogenomic patterns for pediatric cancers. [3] Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 ( EML4 ) gene and the anaplastic lymphoma kinase ( ALK ) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer ( NSCLC ), mostly in non-smokers with adenocarcinoma. [4]nan [1] 在每种情况下，POG 分析都确定了基因组驱动因素，包括新的致癌融合、异常通路和推定的治疗靶点。 [2] 我们证明 RNA-seq 是一种强大的工具，可以识别临床相关和组织学特异性复发突变、新的致癌融合以及儿童癌症的转化相关免疫基因组模式。 [3] 导致棘皮动物微管相关蛋白样 4 (EML4) 基因和间变性淋巴瘤激酶 (ALK) 基因融合的染色体易位已被认为是非小细胞肺癌 (NSCLC) 子集中的一种新型致癌融合。 ，主要发生在患有腺癌的非吸烟者中。 [4]
These Oncogenic Fusion
These oncogenic fusion proteins are tumor-specific, and, therefore, constitute an exceptional target. [1] These oncogenic fusions occur when the kinase domain of NTRK1, NTRK2 or NTRK3 fuse with any of a number of N-terminal partners. [2] These oncogenic fusions occur when the kinase domain of NTRK1, NTRK2 or NTRK3 fuse with any of a number of N-terminal partners. [3]这些致癌融合蛋白是肿瘤特异性的，因此构成了一个特殊的靶点。 [1] 当 NTRK1、NTRK2 或 NTRK3 的激酶结构域与许多 N 末端伙伴中的任何一个融合时，就会发生这些致癌融合。 [2] 当 NTRK1、NTRK2 或 NTRK3 的激酶结构域与许多 N 末端伙伴中的任何一个融合时，就会发生这些致癌融合。 [3]
Tacc3 Oncogenic Fusion
We found that pan-FGFR inhibitors and MEK1/2 inhibitors antagonized the PPARG-driven reporter assay with potency similar to reported values for their cognate targets (1-20 nM) and interestingly, RT112 cells carry an FGFR3-TACC3 oncogenic fusion. [1] Molecular testing was performed and revealed a TERT promotor mutation, an FGFR3-TACC3 oncogenic fusion, and a copy number loss in CDKN2A/CDKN2B. [2]我们发现泛 FGFR 抑制剂和 MEK1/2 抑制剂拮抗 PPARG 驱动的报告基因检测的效力与其同源靶标 (1-20 nM) 的报告值相似，有趣的是，RT112 细胞携带 FGFR3-TACC3 致癌融合。 [1]