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BACKGROUND Next-generation sequencing was performed on pulmonary and pancreatic fine-needle aspirations (FNAs) and on paired FNAs and resected primary tumors from the same patient. METHODS DNA 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). RESULTS Genomic 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. CONCLUSIONS The 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. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state. [ABSTRACT FROM AUTHOR]