Clinical Next-Generation Sequencing Successfully Applied to Fine-Needle Aspirations of Pulmonary and Pancreatic Neoplasms
Clinical Next-Generation Sequencing Successfully Applied to Fine-Needle Aspirations of Pulmonary and Pancreatic Neoplasms
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DOI：
10.1002/cncy.21338
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发表时间：
2013-12-01
影响因子：
3.4
通讯作者：
Ross, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Young, Geneva;Wang, Kai;Ross, Jeffrey S.
方法从16例肺FNAs、23例胰腺FNAs和5例切除的胰腺原发性肿瘤中分离出福尔马林固定、石蜡包埋的细胞块DNA。使用专有测序系统对索引的、衔接子连接的、杂交捕获的文库中的287个癌症相关基因的4561个外显子和19个基因的47个内含子进行了下一代测序（Illumina HiSeq 2000）.从16个（100%）肺FNA中的16个成功地产生了基因组谱，其中非小细胞肺癌（NSCLC）14例，小细胞肺癌（SCLC）2例。NSCLC组包括6例腺癌、5例鳞状细胞癌和3例非小细胞肺癌（未另行说明）。从23例胰腺FNA中的23例（100%）和5例（100%）匹配的胰腺原发性肿瘤中成功获得基因组图谱，其中包括17例导管腺癌，3例粘液腺癌，2例腺癌NOS和1例神经内分泌肿瘤。在16例肺FNA中鉴定出81个基因组改变（平均每例患者5.1个基因组改变）;最常见的基因组改变是TP 53、RB 1、SOX 2、PIK 3CA和KRAS。在23例胰腺肿瘤FNA中鉴定出87个基因组改变（平均每例患者3.8个基因组改变）;最常见的基因组改变是KRAS、TP 53、CDKN 2A/B、SMAD 4和PTEN。在胰腺肿瘤中，有100%的一致性，20个基因组的改变，确定在5名患者匹配的FNA和手术原发性tumor pairs.CONCLUSIONSThe作者能够进行下一代测序可靠的肺和胰腺肿瘤的FNA，和基因组的改变发现相关性以及在匹配的切除胰腺肿瘤中确定。癌症（癌症细胞病理学）2013;121：688-694。(c)2013年美国癌症协会
BACKGROUNDNext-generation sequencing was performed on pulmonary and pancreatic fine-needle aspirations (FNAs) and on paired FNAs and resected primary tumors from the same patient.METHODSDNA was isolated in formalin-fixed, paraffin-embedded cell blocks from 16 pulmonary FNAs, 23 pancreatic FNAs, and 5 resected pancreatic primary tumors. Next-generation sequencing was performed for 4561 exons of 287 cancer-related genes and for 47 introns of 19 genes on indexed, adaptor-ligated, hybridization-captured libraries using a proprietary sequencing system (the Illumina HiSeq 2000).RESULTSGenomic profiles were generated successfully from 16 of 16 (100%) pulmonary FNAs, which included 14 nonsmall cell lung cancers (NSCLCs) and 2 small cell lung cancers (SCLCs). The NSCLC group included 6 adenocarcinomas, 5 squamous cell carcinomas, and 3 NSCLCs not otherwise specified. Genomic profiles were successfully obtained from 23 of 23 (100%) pancreatic FNAs and from 5 of 5 (100%) matched pancreatic primary tumors, which included 17 ductal adenocarcinomas, 3 mucinous adenocarcinomas, 2 adenocarcinomas NOS, and 1 neuroendocrine tumor. Eighty-one genomic alterations were identified in the 16 pulmonary FNAs (average, 5.1 genomic alterations per patient); and the most common genomic alterations were TP53, RB1, SOX2, PIK3CA, and KRAS. Eighty-seven genomic alterations were identified in the 23 pancreatic tumor FNAs (average, 3.8 genomic alterations per patient); and the most common genomic alterations were KRAS, TP53, CDKN2A/B, SMAD4, and PTEN. Among the pancreatic tumors, there was 100% concordance of 20 genomic alterations that were identified in 5 patient-matched FNA and surgical primary tumor pairs.CONCLUSIONSThe authors were able to perform next-generation sequencing reliably on FNAs of pulmonary and pancreatic tumors, and the genomic alterations discovered correlated well with those identified in matched resected pancreatic tumors. Cancer (Cancer Cytopathol) 2013;121:688-694. (c) 2013 American Cancer Society.