Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine.
Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine.
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翻译全外显子组测序（WES）用于前瞻性临床应用可能影响癌症患者的护理；然而，临床实施需要多种创新。这些包括：(1)来自福尔马林固定石蜡包埋（FFPE）肿瘤组织的快速和强大的WES，(2)类似于冷冻样本数据的分析输出，以及(3)对WES数据的临床解释，以供未来使用。在这里，我们描述了一种用于存档FFPE肿瘤样本的前瞻性临床WES平台。该平台采用计算方法对WES数据进行有效的临床分析和解释。当回顾性地应用于511个外显子组时，解释框架揭示了临床重要基因的体细胞改变的“长尾”。该方法的前瞻性应用在15/16例患者中发现了临床相关的改变。在一名患者中，先前未被发现的发现指导了临床试验的入组，导致了客观的临床反应。总的来说，这种方法可以为精确癌症医学的广泛实施提供信息。
Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
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影响因子：
50.3
作者：
Carretero J;Shimamura T;Rikova K;Jackson AL;Wilkerson MD;Borgman CL;Buttarazzi MS;Sanofsky BA;McNamara KL;Brandstetter KA;Walton ZE;Gu TL;Silva JC;Crosby K;Shapiro GI;Maira SM;Ji H;Castrillon DH;Kim CF;García-Echeverría C;Bardeesy N;Sharpless NE;Hayes ND;Kim WY;Engelman JA;Wong KK
通讯作者：
Wong KK
影响因子：
28.2
作者：
Cheung HW;Du J;Boehm JS;He F;Weir BA;Wang X;Butaney M;Sequist LV;Luo B;Engelman JA;Root DE;Meyerson M;Golub TR;Jänne PA;Hahn WC
通讯作者：
Hahn WC
影响因子：
20.3
作者：
Boggon, TJ;Li, YQ;Eck, MJ
通讯作者：
Eck, MJ
影响因子：
12.3
作者：
Fisher S;Barry A;Abreu J;Minie B;Nolan J;Delorey TM;Young G;Fennell TJ;Allen A;Ambrogio L;Berlin AM;Blumenstiel B;Cibulskis K;Friedrich D;Johnson R;Juhn F;Reilly B;Shammas R;Stalker J;Sykes SM;Thompson J;Walsh J;Zimmer A;Zwirko Z;Gabriel S;Nicol R;Nusbaum C
通讯作者：
Nusbaum C
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA