【佳学基因检测】1型神经纤维瘤病样综合征的临床和突变谱

基因变异引起的癌症能医治吗介绍

综述肿瘤的精准化治疗及靶向药物选择《肿瘤靶向药物的敏感性及有效性》《JAMA》在. 2009 Nov 18;302(19):2111-8.发表了一篇题目为《1型神经纤维瘤病样综合征的临床和突变谱》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Ludwine Messiaen , Suxia Yao, Hilde Brems, Tom Callens, Achara Sathienkijkanchai, Ellen Denayer, Emily Spencer, Pamela Arn, Dusica Babovic-Vuksanovic, Carolyn Bay, Gary Bobele, Bruce H Cohen, Luis Escobar, Deborah Eunpu, Theresa Grebe, Robert Greenstein, Rachel Hachen, Mira Irons, David Kronn, Edmond Lemire, Kathleen Leppig, Cynthia Lim, Marie McDonald, Vinodh Narayanan, Amy Pearn, Robert Pedersen, Berkley Powell, Lawrence R Shapiro, David Skidmore, David Tegay, Heidi Thiese, Elaine H Zackai, Raymon Vijzelaar, Koji Taniguchi, Toranoshin Ayada, Fuyuki Okamoto, Akihiko Yoshimura, Annabel Parret, Bruce Korf, Eric Legius等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤是否遗传课题临床研究内容关键词：

咖啡牛奶斑,CALM,腋窝雀斑,大头畸形,NF1,基因检测

肿瘤靶向治疗基因检测临床应用结果

肿瘤基因检测突变类型与相关性研究背景：基因解码已经描述了常染色体显性失活芽孢相关 EVH1 域含蛋白 1 (SPRED1) 突变在主要表现为咖啡牛奶斑 (CALM)、腋窝雀斑和大头畸形的个体中的存在情况。这种新疾病的临床谱范围需要进一步描述。基因检测突变类型与相关性的研究目的：确定大量患者中神经纤维瘤病 1 型样综合征 (NFLS) 的发生率、突变谱和表型。设计、设置和参与者：在一项横断面研究中，23 名通过临床测试确定的携带 SPRED1 突变的无关先证者与其家人一起参与了基因型-表型研究 (2007-2008)。在第二项横断面研究中，对 2003-2007 年从 1 型神经纤维瘤病 (NF1) 中具有广泛症状但未检测到 NF1 种系突变的患者收集的 1318 份不相关的匿名样本进行了 SPRED1 突变分析。主要结果测量：比较有或没有 SPRED1 或 NF1 突变的患者的综合临床特征。功能测定用于评估错义突变的致病性。结果：在来自临床队列的 42 名 SPRED1 阳性个体中，20 名（48%；95% 置信区间 [CI]，32%-64%）符合美国国立卫生研究院（ NIH) NF1 诊断标准基于存在或不存在雀斑或 NF1 兼容家族史的 5 个以上 CALM。 42 名 SPRED1 阳性个体（0%；95% CI，0%-7%）均无离散的皮肤或丛状神经纤维瘤、典型的 NF1 骨性病变或有症状的视神经胶质瘤。在 1318 名个体的匿名队列中，43 名先证者中发现了 34 个不同的 SPRED1 突变：34 名先证者中有 27 个致病突变，9 名先证者中有 7 个可能的非致病性错义突变。在 94 名有或无雀斑且无其他 NF1 特征的家族性 CALM 的先证者中，69 人（73%；95% CI，63%-80%）有 NF1 突变，18 人（19%；95% CI，12%-29%） ) 具有致病性 SPRED1 突变。在匿名队列中，根据NIH标准临床诊断为NF1的个体中有1.9%（95% CI，1.2%-2.9%）患有NFLS。结论：NF1突变阴性家族中SPRED1突变检出率较高。具有 CALM 的常染色体显性表型，有或没有雀斑，没有其他 NF1 特征。在本研究中的个体中，NFLS 与 NF1 中所见的外周和中枢神经系统肿瘤无关。

肿瘤发生与复发转移国际数据库描述：

Context: Autosomal dominant inactivating sprouty-related EVH1 domain-containing protein 1 (SPRED1) mutations have recently been described in individuals presenting mainly with café au lait macules (CALMs), axillary freckling, and macrocephaly. The extent of the clinical spectrum of this new disorder needs further delineation.Objective: To determine the frequency, mutational spectrum, and phenotype of neurofibromatosis type 1-like syndrome (NFLS) in a large cohort of patients.Design, setting, and participants: In a cross-sectional study, 23 unrelated probands carrying a SPRED1 mutation identified through clinical testing participated with their families in a genotype-phenotype study (2007-2008). In a second cross-sectional study, 1318 unrelated anonymous samples collected in 2003-2007 from patients with a broad range of signs typically found in neurofibromatosis type 1 (NF1) but no detectable NF1 germline mutation underwent SPRED1 mutation analysis.Main outcome measures: Comparison of aggregated clinical features in patients with or without a SPRED1 or NF1 mutation. Functional assays were used to evaluate the pathogenicity of missense mutations.Results: Among 42 SPRED1-positive individuals from the clinical cohort, 20 (48%; 95% confidence interval [CI], 32%-64%) fulfilled National Institutes of Health (NIH) NF1 diagnostic criteria based on the presence of more than 5 CALMs with or without freckling or an NF1-compatible family history. None of the 42 SPRED1-positive individuals (0%; 95% CI, 0%-7%) had discrete cutaneous or plexiform neurofibromas, typical NF1 osseous lesions, or symptomatic optic pathway gliomas. In the anonymous cohort of 1318 individuals, 34 different SPRED1 mutations in 43 probands were identified: 27 pathogenic mutations in 34 probands and 7 probable nonpathogenic missense mutations in 9 probands. Of 94 probands with familial CALMs with or without freckling and no other NF1 features, 69 (73%; 95% CI, 63%-80%) had an NF1 mutation and 18 (19%; 95% CI, 12%-29%) had a pathogenic SPRED1 mutation. In the anonymous cohort, 1.9% (95% CI, 1.2%-2.9%) of individuals with the clinical diagnosis of NF1 according to the NIH criteria had NFLS.Conclusions: A high SPRED1 mutation detection rate was found in NF1 mutation-negative families with an autosomal dominant phenotype of CALMs with or without freckling and no other NF1 features. Among individuals in this study, NFLS was not associated with the peripheral and central nervous system tumors seen in NF1.