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右侧结肠癌中的 BRAF V600E 突变:液体活检检测到的异质性。

BRAF V600E mutations in right-side colon cancer: Heterogeneity detected by liquid biopsy.

机构信息

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

出版信息

Eur J Surg Oncol. 2022 Jun;48(6):1375-1383. doi: 10.1016/j.ejso.2022.01.016. Epub 2022 Feb 2.

Abstract

INTRODUCTION

The prognosis for metastatic colorectal cancer patients (mCRC) with the BRAF mutation is poor. BRAF mutation frequency is reportedly low among Asians; however, the frequency of the BRAF mutation in right-side colon cancer may not be low, even among Asians. In addition, spatial heterogeneity of BRAF mutations also exists, as for RAS mutations. In this prospective observational study, we evaluated BRAF mutations in cancer tissue and plasma of Japanese right-side colon cancer patients.

METHOD

215 patients with right-side colon cancer were included. BRAF mutations of cancer tissue and plasma were detected using droplet digital PCR. Blood plasma of patients with BRAF mutations in cancer tissue or plasma was drawn at intervals throughout chemotherapy, and BRAF mutations were evaluated.

RESULTS

BRAF mutations were detected in tissue samples from 35 of 215 patients (16.3%, cecum; 22.4%, ascending colon; 17.8%, and transverse colon; 9.0%). BRAF mutations were detected in plasma of 10 of 215 (4.7%) patients. Eight of the ten patients had BRAF mutations in their primary tumours, but two (both were Stage IV) patients did not. Sensitivity of liquid biopsy to detect BRAF mutations was 10.3% (3/29) in Stage I-III patients and 83.3% (5/6) in Stage IV patients.

CONCLUSION

BRAF mutations are observed in right-side colon cancer at high frequency, especially in the cecum. BRAF mutations can be detected in plasma and the detection rate is high in patients with advanced cancer. Spatial heterogeneity was observed using liquid biopsy.

摘要

简介

BRAF 突变的转移性结直肠癌(mCRC)患者预后较差。据报道,亚洲人中 BRAF 突变的频率较低;然而,即使在亚洲人中,右半结肠癌的 BRAF 突变频率也可能不低。此外,与 RAS 突变一样,BRAF 突变也存在空间异质性。在这项前瞻性观察性研究中,我们评估了日本右半结肠癌患者肿瘤组织和血浆中的 BRAF 突变。

方法

共纳入 215 例右半结肠癌患者。采用液滴数字 PCR 检测肿瘤组织和血浆中的 BRAF 突变。对组织中存在 BRAF 突变的患者的血浆,在整个化疗过程中定期抽取并进行 BRAF 突变评估。

结果

215 例患者中有 35 例(16.3%,盲肠;22.4%,升结肠;17.8%,横结肠;9.0%)组织样本中检测到 BRAF 突变。215 例患者中有 10 例(4.7%)血浆中检测到 BRAF 突变。这 10 例患者中有 8 例存在原发性肿瘤的 BRAF 突变,但有 2 例(均为 IV 期)患者没有。液体活检检测 BRAF 突变的敏感性在 I-III 期患者中为 10.3%(3/29),在 IV 期患者中为 83.3%(5/6)。

结论

右半结肠癌中 BRAF 突变频率较高,尤其是在盲肠。BRAF 突变可在血浆中检测到,晚期癌症患者的检出率较高。液体活检观察到空间异质性。

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