从胰胆管合流异常到胆囊癌的 TP53 突变的逐步相关性：一项回顾性研究。

Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study.

机构信息

First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.

First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

出版信息

BMC Cancer. 2021 Nov 19;21(1):1245. doi: 10.1186/s12885-021-09000-2.

DOI:10.1186/s12885-021-09000-2

PMID:34798839

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8605550/

Abstract

BACKGROUND

The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS).

METHODS

We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status.

RESULTS

The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p < 0.01).

CONCLUSIONS

TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.

摘要

背景

在有胆囊癌（GBC）风险因素的患者中，致癌的遗传变化仍然存在争议，尤其是在具有胰胆管合流异常（PBM）的患者中。本研究旨在使用下一代测序（NGS）阐明 GBC 风险因素与遗传变化之间的关联。

方法

我们回顾性分析了 64 名被诊断为 GBC（n=26）、PBM[伴有 GBC（n=8）、不伴有 GBC（n=20）]和慢性胆囊炎患者的切除组织，这些患者用作对照组（n=10）。使用激光捕获显微切割术从肿瘤及其周围组织中提取 DNA。通过 NGS 检测 50 个与癌症相关的基因的基因改变，并将其与包括 PBM 状态在内的临床信息进行比较。

结果

GBC 组织中最常见的基因改变发生在 TP53（50%），其次是 EGFR（20.6%）、RB1（17.6%）和 ERBB2（17.6%）。在 20 例（58.8%）中检测到可通过分子靶向药物治疗的基因改变。基因改变与风险因素的统计分析表明，PBM 伴 GBC 的患者中 TP53 改变率高于不伴 PBM 的患者（p=0.038），对照组患者的上皮、不伴 GBC 的 PBM 患者的上皮、PBM 伴 GBC 患者的肿瘤旁黏膜和 PBM 伴 GBC 患者的肿瘤组织中的 TP53 突变率分别为 10%、10%、38%和 75%（p<0.01）。