Sequencing of intraductal biopsies is feasible and potentially impacts clinical management of patients with indeterminate biliary stricture and cholangiocarcinoma.
Sequencing of intraductal biopsies is feasible and potentially impacts clinical management of patients with indeterminate biliary stricture and cholangiocarcinoma.
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DOI：
10.1038/s41424-018-0015-6
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发表时间：
2018-04-30
影响因子：
3.6
通讯作者：
Walter D
中科院分区：
文献类型：
--
作者：
Bankov K;Döring C;Schneider M;Hartmann S;Winkelmann R;Albert JG;Bechstein WO;Zeuzem S;Hansmann ML;Peveling-Oberhag J;Walter D
胆管癌（CCA）的明确诊断和治疗管理仍然是一个挑战。本研究的目的是调查导管内活检靶向测序的可行性和对临床管理的潜在影响。对16例临床后期CCA患者的可疑结果的导管内活检进行了靶向测序分析，包括肿瘤和对照良性组织（n = 55个样本）。设计了含有41个基因的CCA特异性测序板，并应用了双链靶向富集。对所有样品成功进行测序。总共鉴定了79个突变，每个肿瘤样本平均检测到1.7个突变（范围0-4），每个活检样本平均检测到2.3个突变（范围0-6），在6/16例病例中鉴定出潜在的治疗相关基因。在14/18例（78%）异型增生或不确定结果的活检中，检测到至少一种突变。大多数突变在手术标本和活检中发现（68%），而28%仅存在于活检中，而4%仅存在于手术肿瘤标本中。导管内活检的靶向测序是可行的，并可能提高诊断率。胆道发育不良的遗传异质性在临床治疗中需要考虑，并需要进一步研究。目前的研究首次证明了导管内活检测序的可行性，这有可能影响胆道发育不良和肿瘤患者的诊断和治疗管理。
Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies. Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied. Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0–4) as well as 2.3 per biopsy (0–6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen. Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation. The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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