RNF43 Mutations in IPMN Cases: A Potential Prognostic Factor
RNF43 Mutations in IPMN Cases: A Potential Prognostic Factor
复制标题
IPMN 病例中的 RNF43 突变：一个潜在的预后因素
DOI：
10.1155/2020/1457452
复制
发表时间：
2020-08-31
影响因子：
2
通讯作者：
Chen, Jie
中科院分区：
文献类型：
--
作者：
Chang, Xiao Yan;Wu, Yan;Chen, Jie
导管内乳头状粘液性肿瘤（IPMN）是一种常见的胰腺前体病变，通常含有KRAS、GNAS和RNF 43突变。为了阐明IPMN的分子特征，我们对61例IPMN福尔马林固定、石蜡包埋（FFPE）标本进行了KRAS、GNAS和RNF 43突变分析。桑格测序法检测KRAS基因第12、13、61位密码子和GNAS基因第201位密码子的突变率。对RNF 43进行下一代测序，并通过桑格测序进一步验证结果。我们分别在35例（57%）和40例（66%）IPMN病例中发现了KRAS和GNAS突变。GNAS突变与形态学亚型显著相关（P < 0.001），肠亚型（93%）比胃（55%）和胰胆亚型（44%）更普遍，但在嗜酸细胞亚型中不存在。RNF 43基因突变5例（8%），均发生在高度异型增生和浸润性病变中（2/5和3/5）。所有5例携带RNF 43突变的病例也表现出GNAS突变。RNF 43突变与侵袭性IPMN患者的预后较差相关（P = 0.002），而KRAS和GNAS突变不影响患者的预后。
An intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precursor lesion, and it often harbors mutations in KRAS, GNAS, and RNF43. To clarify the molecular profiles of IPMNs, we conducted mutation analysis of KRAS, GNAS, and RNF43 in 61 IPMN formalin-fixed, paraffin-embedded (FFPE) specimens. The mutation rates of codons 12, 13, and 61 in KRAS and codon 201 in GNAS were detected by Sanger sequencing. Next-generation sequencing was performed on RNF43, and the results were further verified by Sanger sequencing. We identified KRAS and GNAS mutations in 35 (57%) and 40 (66%) IPMN cases, respectively. GNAS mutations were significantly correlated with the morphologic subtype (P < 0.001) and were more prevalent in the intestinal subtype (93%) than in the gastric (55%) and pancreatobiliary subtypes (44%) but were absent in the oncocytic subtype. RNF43 mutations were found in 5 cases (8%), all of which occurred in high-grade dysplasia and invasive lesions (2/5 and 3/5). All 5 cases harboring RNF43 mutations also exhibited GNAS mutations. RNF43 mutations were associated with a worse prognosis in invasive IPMN patients (P = 0.002), while KRAS and GNAS mutations did not affect the prognosis of patients.