Abstract：
Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers.
Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs.
Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non-EGFR-KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression-related gene mutations were identified in four cases.
Collectively, our data revealed the genomic features of KDD alterations in a multi-cancer cohort, providing more information for the potential treatment application in the KDD carriers.
Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs.
Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non-EGFR-KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression-related gene mutations were identified in four cases.
Collectively, our data revealed the genomic features of KDD alterations in a multi-cancer cohort, providing more information for the potential treatment application in the KDD carriers.
摘要：
背景：激酶结构域重复（KDD）最近被认为是致癌突变，可能与癌症的耐药性有关。
方法：这里，对65例KDD癌症患者的肿瘤组织和/或血浆进行靶向测序。
结果：在多种癌症类型的约0.1%的总人群中发现完整的KDD。EGFRKDD首先在结直肠癌和乳腺癌中被发现，而FGFR2KDD首先在胃癌中发现。与具有非EGFR-KDD的肿瘤相比,具有EGFR-KDD的肿瘤表现出较低的并发TP53基因改变(p=0.03)和稍高的染色体不稳定性(p=0.27)。免疫途径分析进一步揭示了KDD携带者中细胞因子受体途径的富集(93%)。在4例患者中发现了过度进展相关的基因突变。
结论：总的来说，我们的数据揭示了多癌队列中KDD改变的基因组特征，为KDD携带者的潜在治疗应用提供更多信息。
方法：这里，对65例KDD癌症患者的肿瘤组织和/或血浆进行靶向测序。
结果：在多种癌症类型的约0.1%的总人群中发现完整的KDD。EGFRKDD首先在结直肠癌和乳腺癌中被发现，而FGFR2KDD首先在胃癌中发现。与具有非EGFR-KDD的肿瘤相比,具有EGFR-KDD的肿瘤表现出较低的并发TP53基因改变(p=0.03)和稍高的染色体不稳定性(p=0.27)。免疫途径分析进一步揭示了KDD携带者中细胞因子受体途径的富集(93%)。在4例患者中发现了过度进展相关的基因突变。
结论：总的来说，我们的数据揭示了多癌队列中KDD改变的基因组特征，为KDD携带者的潜在治疗应用提供更多信息。
