Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Cancer Biol Ther. 2023 Dec 31;24(1):2184153. doi: 10.1080/15384047.2023.2184153.
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene () that result in the functional loss of the tumor suppressor folliculin. It is classically associated with cutaneous hamartomas, pulmonary cysts with spontaneous pneumothorax, and various renal cancers. In this case, we present a patient initially diagnosed with chromophobe renal cell carcinoma and subsequently found to have colorectal cancer (CRC). The presence of two separate malignancies in a young patient with a strong family history of CRC (father and paternal grandfather) led to genetic testing, which revealed an c.1177-5_1177-3del mutation, and a diagnosis of BHD was made. Out of the more than 300 known unique mutations of the coding region, the c.1285dupC mutation on exon 11 has been the only one convincingly associated with CRC thus far. While larger cohort studies are needed to further clarify this association, we present the first patient with CRC to our knowledge with an c.1177-5_1177-3del mutation and loss of heterozygosity implicating it as an initiating factor in tumorigenesis. We further explore the studies supporting and refuting the connection between BHD and CRC and highlight the molecular signaling pathways that may play a role in pathogenesis.
Birt-Hogg-Dubé 综合征（BHD）是一种常染色体显性遗传疾病，由成纤维细胞瘤基因突变引起，导致肿瘤抑制因子成纤维细胞瘤功能丧失。它通常与皮肤错构瘤、自发性气胸的肺囊肿和各种肾癌有关。在本例中，我们报告了 1 例最初诊断为嫌色细胞肾细胞癌，随后发现结直肠癌（CRC）的患者。一位年轻患者同时患有两种不同的恶性肿瘤，且该患者有强烈的 CRC 家族史（父亲和祖父），这促使进行了基因检测，结果显示存在 c.1177-5_1177-3del 突变，从而做出了 BHD 的诊断。在已知的 编码区的 300 多种独特突变中，迄今为止，exon 11 上的 c.1285dupC 突变是唯一与 CRC 明确相关的突变。虽然需要更大的队列研究来进一步阐明这种关联，但我们报告了首例已知携带 c.1177-5_1177-3del 突变和杂合性丢失的 CRC 患者，这表明该突变可能是肿瘤发生的起始因素。我们进一步探讨了支持和反驳 BHD 与 CRC 之间关联的研究，并强调了可能在发病机制中起作用的分子信号通路。
