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Molecular Analysis of a Patient With Neurofibromatosis 2 (NF2) and Peritoneal Malignant Mesothelioma.

神经纤维瘤病 2 (NF2) 和腹膜恶性间皮瘤患者的分子分析。

  • 影响因子:6.06
  • DOI:10.1097/PAS.0000000000001359
  • 作者列表:"Glass C","Sholl LM","Landgraf JR","Chirieac L","Roggli VL
  • 发表时间:2020-02-01
Abstract

:Neurofibromatosis type 2 (NF2), an inherited disorder associated with multiple inherited schwannomas, meningiomas and ependymomas is caused by an autosomal dominant, likely loss of function germline mutation of the NF2 gene. Interestingly, biallelic NF2 gene inactivation is one of the most common mutations associated with the development of malignant mesothelioma (MM), a highly fatal malignancy that arises in the pleura and less frequently in the pericardium, peritoneum, and tunica vaginalis. It has been proposed that NF2 patients could potentially be at increased risk of developing MM. However, patients with inherited NF2 rarely develop MM. To date, only 2 cases describing patients diagnosed with both have been reported in the literature. Here, we describe the third case and for the first time, also provide molecular evidence that a "second hit" involving a somatic mutation is likely required to trigger the development of MM in this rare cohort. In our patient diagnosed with NF2 at age 25 who developed an aggressive peritoneal MM 15 years later, we identified a germline NF2 mutation and somatic mutations including BAP1. Of clinical relevance, our case supports a germline NF2 mutation may not necessarily be more susceptible to develop mesothelioma without a "second hit" mutation.

摘要

: 神经纤维瘤病 2 型 (NF2),一种与多个遗传性神经鞘瘤、脑膜瘤和室管膜瘤相关的遗传性疾病,由常染色体显性遗传,可能丧失NF2 基因的种系功能突变引起。有趣的是,双等位基因NF2 基因失活是与恶性间皮瘤 (MM) 的发展相关的最常见的突变之一,这是一种高度致命的恶性肿瘤,出现在胸膜,心包较少,腹膜和鞘膜。已经提出,NF2 患者可能具有发展MM的潜在风险增加。然而,遗传性NF2 患者很少发生MM。迄今为止,文献中仅报道了 2 例描述诊断为两者的患者。在这里,我们描述了第三个案例,第一次,还提供了分子证据,表明在这个罕见的队列中,可能需要涉及体细胞突变的 “第二次命中” 来触发MM的发展。在我们 25 岁诊断为NF2 的患者中,15 年后出现侵袭性腹膜MM,我们鉴定了种系NF2 突变和体细胞突变,包括bap1。就临床意义而言,我们的病例支持种系NF2 突变不一定更容易发生间皮瘤而没有 “二次命中” 突变。

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DOI:10.1016/j.athoracsur.2019.04.100
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METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

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影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

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影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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