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所有突变都一样吗?一例转移性结肠腺癌患者同时存在相互排斥的KRAS和BRAF突变的罕见病例报告。

Are All Mutations the Same? A Rare Case Report of Coexisting Mutually Exclusive KRAS and BRAF Mutations in a Patient with Metastatic Colon Adenocarcinoma.

作者信息

Vittal Anusha, Middinti Akshay, Kasi Loknath Kumar Anup

机构信息

Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Division of Medical Oncology, University of Kansas Medical Center, Kansas City, KS, USA.

出版信息

Case Rep Oncol Med. 2017;2017:2321052. doi: 10.1155/2017/2321052. Epub 2017 Jul 24.

Abstract

29-year-old Hispanic woman presented to the clinic with complaints of abdominal pain, nausea, fatigue, and constipation. Laboratory tests indicated the presence of iron deficiency anemia and transaminitis. Imaging evaluation revealed marked hepatomegaly with multiple hepatic metastases and pelvic lymphadenopathy. Biopsy of the hepatic lesions showed adenocarcinoma positive for pan-cytokeratin, CMA5.2, villin, and CDX2. She was positive for tumor markers CA 19-9, CA-125, and CEA. Upon further evaluation, she was found to have colorectal cancer positive for KRAS and BRAF mutations. Unfortunately, her disease progressed rapidly and she expired within 3 months from the time of her first diagnosis. KRAS and BRAF mutations are rare enough to be considered virtually mutually exclusive but coexistent mutations appear to be a distinct molecular and clinical subset with aggressive course of illness, which is in dire need of new treatment strategies. Panitumumab and Cetuximab are approved for patients with wild type KRAS CRC. Vemurafenib is a potent inhibitor of the kinase domain in mutant BRAF and its use in BRAF mutated colon cancer remains to be well established. Our report highlights the need to obtain tissue samples from these patients for analysis and to evaluate the benefit of Vemurafenib in colorectal cancers.

摘要

一名29岁的西班牙裔女性因腹痛、恶心、疲劳和便秘前往诊所就诊。实验室检查显示存在缺铁性贫血和转氨酶升高。影像学评估显示肝脏明显肿大,伴有多处肝转移和盆腔淋巴结病。肝脏病变活检显示腺癌,全细胞角蛋白、CMA5.2、绒毛蛋白和CDX2呈阳性。她的肿瘤标志物CA 19-9、CA-125和CEA呈阳性。进一步评估发现,她患有KRAS和BRAF突变阳性的结直肠癌。不幸的是,她的病情进展迅速,自首次诊断后3个月内死亡。KRAS和BRAF突变极为罕见,几乎可视为相互排斥,但共存突变似乎是一个具有侵袭性病程的独特分子和临床亚组,急需新的治疗策略。帕尼单抗和西妥昔单抗被批准用于野生型KRAS结直肠癌患者。维莫非尼是突变型BRAF激酶结构域的强效抑制剂,其在BRAF突变型结肠癌中的应用仍有待充分确立。我们的报告强调了从这些患者获取组织样本进行分析以及评估维莫非尼在结直肠癌中的益处的必要性。

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