【佳學(xué)基因檢測】1型神經(jīng)纖維瘤病樣綜合征的臨床和突變譜

基因變異引起的癌癥能醫(yī)治嗎介紹

綜述腫瘤的正確化治療及靶向藥物選擇《腫瘤靶向藥物的敏感性及有效性》《JAMA》在.?2009 Nov 18;302(19):2111-8.發(fā)表了一篇題目為《1型神經(jīng)纖維瘤病樣綜合征的臨床和突變譜》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由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。促進(jìn)了腫瘤的正確治療與個性化用藥的發(fā)展，進(jìn)一步強調(diào)了基因信息檢測與分析的重要性。

腫瘤是否遺傳課題臨床研究內(nèi)容關(guān)鍵詞：

咖啡牛奶斑,CALM,腋窩雀斑,大頭畸形,NF1,基因檢測

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

腫瘤基因檢測突變類型與相關(guān)性研究背景：基因解碼已經(jīng)描述了常染色體顯性失活芽孢相關(guān) EVH1 域含蛋白 1 (SPRED1) 突變在主要表現(xiàn)為咖啡牛奶斑 (CALM)、腋窩雀斑和大頭畸形的個體中的存在情況。這種新疾病的臨床譜范圍需要進(jìn)一步描述?；驒z測突變類型與相關(guān)性的研究目的：確定大量患者中神經(jīng)纖維瘤病 1 型樣綜合征 (NFLS) 的發(fā)生率、突變譜和表型。設(shè)計、設(shè)置和參與者：在一項橫斷面研究中，23 名通過臨床測試確定的攜帶 SPRED1 突變的無關(guān)先證者與其家人一起參與了基因型-表型研究 (2007-2008)。在第二項橫斷面研究中，對 2003-2007 年從 1 型神經(jīng)纖維瘤病 (NF1) 中具有廣泛癥狀但未檢測到 NF1 種系突變的患者收集的 1318 份不相關(guān)的匿名樣本進(jìn)行了 SPRED1 突變分析。主要結(jié)果測量：比較有或沒有 SPRED1 或 NF1 突變的患者的綜合臨床特征。功能測定用于評估錯義突變的致病性。結(jié)果：在來自臨床隊列的 42 名 SPRED1 陽性個體中，20 名（48%；95% 置信區(qū)間 [CI]，32%-64%）符合美國國立衛(wèi)生研究院（ NIH) NF1 診斷標(biāo)準(zhǔn)基于存在或不存在雀斑或 NF1 兼容家族史的 5 個以上 CALM。 42 名 SPRED1 陽性個體（0%；95% CI，0%-7%）均無離散的皮膚或叢狀神經(jīng)纖維瘤、典型的 NF1 骨性病變或有癥狀的視神經(jīng)膠質(zhì)瘤。在 1318 名個體的匿名隊列中，43 名先證者中發(fā)現(xiàn)了 34 個不同的 SPRED1 突變：34 名先證者中有 27 個致病突變，9 名先證者中有 7 個可能的非致病性錯義突變。在 94 名有或無雀斑且無其他 NF1 特征的家族性 CALM 的先證者中，69 人（73%；95% CI，63%-80%）有 NF1 突變，18 人（19%；95% CI，12%-29%） ) 具有致病性 SPRED1 突變。在匿名隊列中，根據(jù)NIH標(biāo)準(zhǔn)臨床診斷為NF1的個體中有1.9%（95% CI，1.2%-2.9%）患有NFLS。結(jié)論：NF1突變陰性家族中SPRED1突變檢出率較高。具有 CALM 的常染色體顯性表型，有或沒有雀斑，沒有其他 NF1 特征。在本研究中的個體中，NFLS 與 NF1 中所見的外周和中樞神經(jīng)系統(tǒng)腫瘤無關(guān)。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

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.