【佳學(xué)基因檢測】晚期前列腺癌的靶向下一代測序確定潛在的治療靶點(diǎn)和疾病異質(zhì)性

靶向治療基因檢測醫(yī)保報(bào)銷嗎—揭密

討化基因檢測機(jī)構(gòu)自我培訓(xùn)教材《腫瘤基因易感位點(diǎn)列表及發(fā)生率分析》《Eur Urol》在.?2013 May;63(5):920-6.發(fā)表了一篇題目為《晚期前列腺癌的靶向下一代測序確定潛在的治療靶點(diǎn)和疾病異質(zhì)性》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Himisha Beltran,?Roman Yelensky,?Garrett M Frampton,?Kyung Park,?Sean R Downing,?Theresa Y MacDonald,?Mirna Jarosz,?Doron Lipson,?Scott T Tagawa,?David M Nanus,?Philip J Stephens,?Juan Miguel Mosquera,?Maureen T Cronin,?Mark A Rubin等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

共同裝載,聯(lián)合治療,高效轉(zhuǎn)染,外泌體,腫瘤靶向

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

基因解碼基因檢測的研究介紹：大多數(shù)涉及 DNA 測序的個(gè)性化癌癥護(hù)理策略高度依賴于獲得足夠的新鮮或冷凍組織。由于轉(zhuǎn)移組織的獲取有限，全面評估晚期前列腺癌 (PCa) 的基因組一直具有挑戰(zhàn)性?；蚪獯a基因檢測的研究目的：證明可與檔案福爾馬林一起使用的新型下一代測序 (NGS) 平臺的可行性- 固定石蠟包埋 (FFPE) 活檢組織，以評估晚期 PCa 中所見的 DNA 改變譜。設(shè)計(jì)、設(shè)置和參與者：FFPE 樣本（包括檔案前列腺切除術(shù)和前列腺針活檢）來自代表疾病譜的 45 名患者：局部 PCa、轉(zhuǎn)移性激素初治 PCa 和轉(zhuǎn)移性去勢抵抗性 PCa (CRPC)?；蚪獯a基因檢測還評估了成對的原發(fā)灶和轉(zhuǎn)移灶，以了解疾病異質(zhì)性和疾病進(jìn)展。干預(yù)：從 FFPE 樣本中提取至少 50 ng 的腫瘤 DNA，并使用 Illumina HiSeq 2000 平臺用于雜交捕獲和 NGS?；蚪獯a基因檢測的研究結(jié)果測量和統(tǒng)計(jì)分析：A評估了 182 個(gè)癌癥相關(guān)基因的 3320 個(gè)外顯子和 14 個(gè)常見重排基因的 37 個(gè)內(nèi)含子的基因組改變。基因解碼基因檢測的研究結(jié)果和局限性：基因解碼基因檢測獲得了 >900X 的平均測序深度?？傮w而言，44% 的 CRPC 存在涉及雄激素受體基因 (AR) 的基因組改變，包括 AR 拷貝數(shù)增加（24% 的 CRPC）或 AR 點(diǎn)突變（20% 的 CRPC）。其他經(jīng)常發(fā)生的突變包括跨膜蛋白酶、絲氨酸 2 基因 (TMPRSS2):v-ets erythroblastosis virus E26 癌基因同源物（禽）基因 (ERG) 融合 (44%)；磷酸酶和張力蛋白同源基因（PTEN）丟失（44%）；腫瘤蛋白p53基因（TP53）突變（40%）；視網(wǎng)膜母細(xì)胞瘤基因（RB）缺失（28%）； v-myc 骨髓細(xì)胞瘤病病毒癌基因同源物（禽）基因（MYC）增益（12%）；和 phosphatidylinositol-4,5-bisphosphate 3-kinase，催化亞基 α 基因 (PIK3CA) 突變 (4%)。涉及對 DNA 修復(fù)很重要的關(guān)鍵基因的基因組改變的發(fā)生率很高，包括乳腺癌 2、早發(fā)基因 (BRCA2) 丟失 (12%) 和共濟(jì)失調(diào)毛細(xì)血管擴(kuò)張癥突變基因 (ATM) 突變 (8%)；這些改變可能是聚（二磷酸腺苷 - 核糖）聚合酶抑制劑的靶向。還檢測到涉及 v-raf 鼠肉瘤病毒癌基因同源物 B1 基因 (BRAF) 的新穎且可操作的重排。

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

Background:?Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue.Objective:?To demonstrate the feasibility of a novel next-generation sequencing (NGS)-based platform that can be used with archival formalin-fixed paraffin-embedded (FFPE) biopsy tissue to evaluate the spectrum of DNA alterations seen in advanced PCa.Design, setting, and participants:?FFPE samples (including archival prostatectomies and prostate needle biopsies) were obtained from 45 patients representing the spectrum of disease: localized PCa, metastatic hormone-naive PCa, and metastatic castration-resistant PCa (CRPC). We also assessed paired primaries and metastases to understand disease heterogeneity and disease progression.Intervention:?At least 50 ng of tumor DNA was extracted from FFPE samples and used for hybridization capture and NGS using the Illumina HiSeq 2000 platform.Outcome measurements and statistical analysis:?A total of 3320 exons of 182 cancer-associated genes and 37 introns of 14 commonly rearranged genes were evaluated for genomic alterations.Results and limitations:?We obtained an average sequencing depth of >900X. Overall, 44% of CRPCs harbored genomic alterations involving the androgen receptor gene (AR), including AR copy number gain (24% of CRPCs) or AR point mutation (20% of CRPCs). Other recurrent mutations included transmembrane protease, serine 2 gene (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) gene (ERG) fusion (44%); phosphatase and tensin homolog gene (PTEN) loss (44%); tumor protein p53 gene (TP53) mutation (40%); retinoblastoma gene (RB) loss (28%); v-myc myelocytomatosis viral oncogene homolog (avian) gene (MYC) gain (12%); and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α gene (PIK3CA) mutation (4%). There was a high incidence of genomic alterations involving key genes important for DNA repair, including breast cancer 2, early onset gene (BRCA2) loss (12%) and ataxia telangiectasia mutated gene (ATM) mutations (8%); these alterations are potentially targetable with poly(adenosine diphosphate-ribose)polymerase inhibitors. A novel and actionable rearrangement involving the v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) was also detected.