Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.
Pathol Res Pract. 2024 Sep;261:155473. doi: 10.1016/j.prp.2024.155473. Epub 2024 Jul 24.
The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers.
From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified.
Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1.
Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.
克氏大鼠肉瘤病毒（KRAS）是一种重要的原癌基因。已经开发出几种针对 KRAS 突变的治疗方法。然而，KRAS 扩增，即 KRAS 改变，目前了解甚少，除了常规化疗外，尚无其他合适的治疗方法。本研究旨在阐明 KRAS 扩增在不同类型癌症中的作用。
2019 年 10 月至 2023 年 6 月，我们在三星医疗中心对 37 种不同癌症类型的 3895 名患者使用 Trusight Oncology 500 进行了下一代测序。我们根据癌症类型分析了 KRAS 扩增的分布及其与肿瘤突变负担（TMB）的相关性。同时还鉴定了伴随的 KRAS 突变。
在总共 3895 名患者中，有 99 名（2.5%）存在 KRAS 扩增。在结直肠癌患者中，KRAS 扩增的频率最高，为 2%（27/1350），其次是胃癌患者（3.48%，32/920）和胰腺癌患者（3.88%，9/232）。在存在 KRAS 扩增的患者中，MSI-High 未检出。KRAS 拷贝数变异与 TMB 状态之间没有相关性。在有 KRAS 扩增的患者中，有 27.3%（27/99）同时存在 KRAS 突变。超过 50%的患者存在 G12D 或 G12V 突变。在胃癌中，同时存在 KRAS 扩增和突变的患者极其罕见，为 3.1%（1/32）；然而，在结直肠癌中，超过一半的患者存在 KRAS 扩增和突变（51.9%，14/27）。KRAS 扩增和突变与肿瘤抑制基因 TP53、BRCA2、ARID1B 和 PTCH1 的突变有关。
在 3895 名转移性实体瘤患者中，有 99 名（2.5%）存在 KRAS 扩增，通过下一代测序分析，我们对 KRAS 扩增有了更深入的了解。
