Wang Liang-Li, Zheng Wei, Liu Xiu-Li, Yin Feng
Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, United States.
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, United States.
World J Clin Oncol. 2022 Oct 24;13(10):779-788. doi: 10.5306/wjco.v13.i10.779.
The FAT cadherin family members (FAT1, FAT2, FAT3 and FAT4) are conserved tumor suppressors that are recurrently mutated in several types of human cancers, including colorectal carcinoma (CRC).
To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.
We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset. CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in , , and . Individual clinicopathological data were collected after digital slide review. Statistical analysis was performed using tests and chi-square tests.
This CRC study cohort had frequent mutations in the (10.5%), (11.2%), (15.4%) and (23.4%) genes. Two hundred CRC patients (38.0%) harbored somatic mutations in one or more of the family genes and were grouped into the FAT mutated CRC subtype. The FAT-mutated CRC subtype was more commonly located on the right side of the colon (51.0%) than in the rest of the cohort (30.1%, < 0.001). It showed favorable clinicopathologic features, including a lower rate of positive lymph nodes (pN1-2: 33.5% 46.4%, = 0.005), a lower rate of metastasis to another site or organ (pM1: 7.5% 16.3%, = 0.006), and a trend toward an early tumor stage (pT1-2: 25.0% 18.7%, = 0.093). FAT somatic mutations were significantly enriched in microsatellite instability CRC (28.0% 2.1%, < 0.001). However, FAT somatic mutations in microsatellite stable CRC demonstrated similar clinicopathologic behaviors, as well as a trend of a better disease-free survival rate (hazard ratio = 0.539; 95% confidence interval: 0.301-0.967; log-rank = 0.073).
cadherin family genes are frequently mutated in CRC, and their mutation profile defines a subtype of CRC with favorable clinicopathologic characteristics.
FAT 钙黏蛋白家族成员（FAT1、FAT2、FAT3 和 FAT4）是保守的肿瘤抑制因子，在包括结直肠癌（CRC）在内的几种人类癌症中经常发生突变。
描述 FAT 钙黏蛋白家族成员发生体细胞突变的 CRC 患者的临床病理特征。
我们分析了来自癌症基因组图谱泛癌图谱数据集的 526 例 CRC 病例。根据 FAT1、FAT2、FAT3 和 FAT4 中是否存在体细胞突变，将 CRC 样本分为两组。在数字玻片检查后收集个体临床病理数据。使用 t 检验和卡方检验进行统计分析。
该 CRC 研究队列中，FAT1（10.5%）、FAT2（11.2%）、FAT3（15.4%）和 FAT4（23.4%）基因频繁发生突变。200 例 CRC 患者（38.0%）在一个或多个 FAT 家族基因中存在体细胞突变，并被归入 FAT 突变型 CRC 亚型。FAT 突变型 CRC 亚型在结肠右侧的分布更为常见（51.0%），高于队列其他部分（30.1%，P<0.001）。它表现出良好的临床病理特征，包括较低的阳性淋巴结率（pN1-2：33.5%对 46.4%，P = 0.005）、较低的转移至其他部位或器官的发生率（pM1：7.5%对 16.3%，P = 0.006），以及早期肿瘤阶段的趋势（pT1-2：25.0%对 18.7%，P = 0.093）。FAT 体细胞突变在微卫星不稳定 CRC 中显著富集（28.0%对 2.1%，P<0.001）。然而，微卫星稳定 CRC 中的 FAT 体细胞突变表现出相似的临床病理行为，以及无病生存率更好的趋势（风险比 = 0.539；95%置信区间：0.301-0.967；对数秩 P = 0.073）。
FAT 钙黏蛋白家族基因在 CRC 中频繁突变，其突变谱定义了一种具有良好临床病理特征的 CRC 亚型。
