多发性腺瘤性息肉和锯齿状息肉患者中 MUTYH 相关息肉的患病率和特征。

Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps.

机构信息

Authors' Affiliations: Unidad de Investigación, Departments of Pathology, and Gastroenterology, Hospital General Universitario, Alicante; Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense; Department of Gastroenterology, Bellvitge University Hospital; Institut de Malaties Digestives i Metabòliques, CIBERehd, Hospital Clínic; Department of Oncology, Hospital Vall d'Hebrón, Barcelona; Gastroenterology Department, Complexo Hospitalario de Vigo, Vigo; Department of Gastroenterology, Hospital Donostia, CIBERehd, Universidad del País Vasco, San Sebastián; Department of Gastroenterology, Hospital Universitario de Canarias, La Laguna, Tenerife; Department of Gastroenterology, Clínica Universitaria de Navarra, Pamplona; Department of Gastroenterology, Hospital Mútua de Terrassa, Terrassa; Department of Gastroenterology, Hospital Puerta de Hierro, Madrid; Department of Oncology, Hospital Arnau de Vilanova, Lleida; Department of Gastroenterology, Hospital Bidasoa, Irún; Department of Gastroenterology, Hospital Universitario Virgen del Rocío, Sevilla; Department of Gastroenterology, Hospital Basurto, Bilbao; Department of Molecular Genetics, Hospital General Universitario, Elche, Spain; and Gastrointestinal Cancer Research Laboratory, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

出版信息

Clin Cancer Res. 2014 Mar 1;20(5):1158-68. doi: 10.1158/1078-0432.CCR-13-1490. Epub 2014 Jan 27.

DOI:10.1158/1078-0432.CCR-13-1490

PMID:24470512

Abstract

PURPOSE

The present study aimed to determine the prevalence of MUTYH mutations in patients with multiple colonic polyps and to explore the best strategy for diagnosing MUTYH-associated polyposis (MAP) in these patients.

EXPERIMENTAL DESIGN

This study included 405 patients with at least 10 colonic polyps each. All cases were genetically tested for the three most frequent MUTYH mutations. Whole-gene analysis was performed in heterozygous patients and in 216 patients lacking the three most frequent mutations. Polyps from 56 patients were analyzed for the KRAS-Gly12Cys and BRAF V600E somatic mutations.

RESULTS

Twenty-seven (6.7%) patients were diagnosed with MAP, of which 40.8% showed serrated polyps. The sensitivity of studying only the three common variants was 74.1%. Of 216 patients without any monoallelic mutation in common variants, whole-gene analysis revealed biallelic pathogenic mutation in only one. G396D mutation was associated with serrated lesions and older age at diagnosis. There was a strong association between germinal MUTYH mutation and KRAS Gly12Cys somatic mutation in polyps. BRAF V600E mutation was found in 74% of serrated polyps in MUTYH-negative patients and in none of the polyps of MAP patients.

CONCLUSIONS

We observed a low frequency of MUTYH mutations among patients with multiple adenomatous and serrated polyps. The MAP phenotype frequently included patients with serrated polyps, especially when G396D mutation was involved. Our results show that somatic molecular markers of polyps can be useful in identifying MAP cases and support the need for the complete MUTYH gene analysis only in patients heterozygous for recurrent variants.

摘要

目的

本研究旨在确定多发性结肠息肉患者中 MUTYH 突变的流行率，并探讨在这些患者中诊断 MUTYH 相关息肉病（MAP）的最佳策略。

实验设计

本研究纳入了 405 名每个患者至少有 10 个结肠息肉的患者。所有病例均进行了三种最常见的 MUTYH 突变的基因检测。在杂合子患者和 216 名缺乏三种最常见突变的患者中进行了全基因分析。对 56 名患者的息肉进行了 KRAS-Gly12Cys 和 BRAF V600E 体细胞突变分析。

结果

27 名（6.7%）患者被诊断为 MAP，其中 40.8%表现为锯齿状息肉。仅研究三种常见变异体的敏感性为 74.1%。在 216 名没有任何常见变异体单等位基因突变的患者中，全基因分析仅发现一个双等位致病性突变。G396D 突变与锯齿状病变和诊断时年龄较大有关。在息肉中，生殖细胞 MUTYH 突变与 KRAS Gly12Cys 体细胞突变之间存在很强的关联。在 MUTYH 阴性患者的锯齿状息肉中发现了 74%的 BRAF V600E 突变，而在 MAP 患者的息肉中均未发现。