Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Genetic Diagnosis, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Int J Cancer. 2019 Nov 1;145(9):2488-2495. doi: 10.1002/ijc.32320. Epub 2019 May 7.
The Raf murine sarcoma viral oncogene homolog B (BRAF ) mutation (MT) in metastatic colorectal cancer (CRC) is a well-known prognostic indicator and a negative predictive biomarker for antiepidermal growth factor receptor (EGFR) treatment. However, the clinical characteristics and significance of BRAF MTs remain unclear. Here, we evaluated the clinical characteristics of BRAF MTs vs. those of other MTs in the EGFR signaling pathway, including BRAF . Consecutive CRC patients in our institute from June 2012 to November 2013 were enrolled in our study. Multiplex genotyping of the EGFR pathway was performed with archival samples using a Luminex Assay for BRAF /BRAF , KRAS/NRAS exons 2-4, and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA). We analyzed correlations among the MT profiles, clinical data and primary tumor locations in CRC. All statistical analyses were performed using R software. CRC samples (824) from 374 (45.4%) male and 450 (54.6%) female patients were analyzed, of which 154 (18.7%), 202 (24.5%), 270 (32.8%) or 198 (24.0%) had Stages I, II, III or IV or recurrent CRC, respectively. The frequencies of BRAF /BRAF , KRAS (including exons 2-4), NRAS and PIK3CA MTs were 5.3/1.7, 41.4, 3.3 and 9.6%, respectively. The characteristics of patients with the BRAF MT were an age of ≥65 years old, a right-sided primary tumor location, poorly differentiated histology and an advanced disease stage. In contrast, the characteristics of patients with BRAF MTs were a left-sided primary tumor location and well-differentiated histology. BRAF MTs were relatively rare and showed different characteristics compared to the BRAF MT. These results may contribute to future precision medicine.
Raf 鼠肉瘤病毒癌基因同源物 B（BRAF）突变（MT）在转移性结直肠癌（CRC）中是一个众所周知的预后指标和抗表皮生长因子受体（EGFR）治疗的负预测生物标志物。然而，BRAF MT 在 EGFR 信号通路中的临床特征和意义仍不清楚。在这里，我们评估了 BRAF MT 与 EGFR 信号通路中其他 MT（包括 BRAF、KRAS/NRAS 外显子 2-4 和磷脂酰肌醇-4,5-二磷酸 3-激酶，催化亚单位α（PIK3CA））的临床特征。我们使用 Luminex 分析 BRAF /BRAF、KRAS/NRAS 外显子 2-4 和磷脂酰肌醇-4,5-二磷酸 3-激酶，催化亚单位α（PIK3CA）对我院 2012 年 6 月至 2013 年 11 月连续的 CRC 患者的存档样本进行了 EGFR 通路的多重基因分型。我们分析了 CRC 中 MT 谱、临床数据和原发肿瘤位置之间的相关性。所有统计分析均使用 R 软件进行。分析了 374 名男性（45.4%）和 450 名女性（54.6%）CRC 样本（824 个），其中 154 个（18.7%）、202 个（24.5%）、270 个（32.8%）或 198 个（24.0%）分别患有 I、II、III 或 IV 期或复发性 CRC。BRAF /BRAF、KRAS（包括外显子 2-4）、NRAS 和 PIK3CA MT 的频率分别为 5.3/1.7、41.4、3.3 和 9.6%。具有 BRAF MT 的患者的特征为年龄≥65 岁、右侧原发肿瘤位置、低分化组织学和晚期疾病阶段。相比之下，具有 BRAF MT 的患者的特征为左侧原发肿瘤位置和高分化组织学。BRAF MT 相对较少，与 BRAF MT 相比具有不同的特征。这些结果可能有助于未来的精准医学。
