Department of Surgery, Masaka Regional Referral Hospital, Masaka, Uganda.
Department of Surgery, Faculty of Health Sciences, Equator University of Science and Technology, Masaka, Uganda.
BMC Cancer. 2024 Sep 30;24(1):1212. doi: 10.1186/s12885-024-12967-3.
Uganda is a developing low-income country with a low incidence of colorectal cancer, which is steadily increasing. Ugandan colorectal cancer (CRC) patients are young and present with advanced-stage disease. In our population, there is a scarcity of genetic oncological studies, therefore, we investigated the mutational status of CRC tissues, focusing in particular on the adenomatous polyposis coli (APC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and SMAD4 genes. Our objective was to determine whether there were any differences between other populations and Ugandan patients. We performed next-generation sequencing on the extracted DNA from formalin-fixed paraffin-embedded adenocarcinoma samples from 127 patients (mean (SD) age: 54.9 (16.0) years; male:female sex ratio: 1.2:1). Most tumours were located in the rectum 56 (44.1%), 14 (11%) tumours were high grade, and 96 (75.6%) were moderate grade CRC. Stage III + IV CRC tumours were found in 109 (85.8%) patients. We identified 48 variants of APC, including 9 novel APC mutations that were all pathogenic or deleterious. For PIK3CA, we found 19 variants, of which 9 were deleterious or pathogenic. Four PIK3CA novel pathogenic or deleterious variants were included (c.1397C > G, c.2399_2400insA, c.2621G > C, c.2632C > G). Three SMAD4 variants were reported, including two pathogenic or deleterious variants (c.1268G > T, c.556dupC) and one tolerant (c.563A > C) variant. One novel SMAD4 deleterious mutation (c.1268G > T) was reported. In conclusion, we provide clinicopathological information and new genetic variation data pertinent to CRC in Uganda.
乌干达是一个发展中国家，收入较低，结直肠癌发病率低，但呈稳步上升趋势。乌干达结直肠癌（CRC）患者较为年轻，且疾病已发展至晚期。在我们的人群中，缺乏遗传肿瘤学研究，因此，我们调查了结直肠癌组织的突变状态，特别关注腺瘤性结肠息肉病（APC）、磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位α（PIK3CA）和 SMAD4 基因。我们的目的是确定是否与其他人群存在差异。我们对 127 名患者（平均（SD）年龄：54.9（16.0）岁；男女比例：1.2:1）的福尔马林固定石蜡包埋腺癌样本提取的 DNA 进行了下一代测序。大多数肿瘤位于直肠 56 例（44.1%），14 例（11%）肿瘤为高级别，96 例（75.6%）为中级别 CRC。III+IV 期 CRC 肿瘤在 109 例（85.8%）患者中发现。我们鉴定了 48 种 APC 变体，包括 9 种新的 APC 突变，均为致病性或有害性突变。对于 PIK3CA，我们发现了 19 种变体，其中 9 种为有害或致病性变体。包括 4 种新的致病性或有害性 PIK3CA 变体（c.1397C>G、c.2399_2400insA、c.2621G>C、c.2632C>G）。报道了 3 种 SMAD4 变体，包括 2 种致病性或有害性变体（c.1268G>T、c.556dupC）和 1 种耐受性变体（c.563A>C）。报道了一种新的 SMAD4 有害突变（c.1268G>T）。总之，我们提供了与乌干达 CRC 相关的临床病理信息和新的遗传变异数据。
