中国人种多种癌症中激酶结构域重复的临床和分子特征。
Clinical and molecular characteristics of kinase domain duplications across diverse cancer types in the Chinese population.
机构信息
Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
出版信息
Cancer Med. 2023 Mar;12(5):6009-6015. doi: 10.1002/cam4.5325. Epub 2022 Nov 3.
BACKGROUND
Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers.
METHOD
Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs.
RESULT
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.
CONCLUSION
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.
背景
激酶结构域重复（KDD）最近被认为是致癌突变，并可能与癌症中的耐药性有关。
方法
在这里，对 65 名 KDD 癌症患者的肿瘤组织和/或血浆进行了靶向测序。
结果
在多种癌症类型中，完整的 KDD 约占总人口的 0.1%。EGFR KDD 首先在结直肠癌和乳腺癌中被发现，而 FGFR2 KDD 首先在胃癌中被发现。与非 EGFR-KDD 肿瘤相比，EGFR KDD 肿瘤的 TP53 基因改变（p=0.03）略低，染色体不稳定性（p=0.27）略高。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%）。在四个病例中发现了与超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了更多信息。
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