Genome‐wide identification of genes with amplification and/or fusion in small cell lung cancer. Issue 9 (28th May 2013)

• Record Type: Journal Article
• Authors: Iwakawa, Reika; Takenaka, Masataka; Kohno, Takashi; Shimada, Yoko; Totoki, Yasushi; Shibata, Tatsuhiro; Tsuta, Koji; Nishikawa, Ryo; Noguchi, Masayuki; Sato‐Otsubo, Aiko; Ogawa, Seishi; Yokota, Jun
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 9(2013:Sep.)
• Page Start: 802
• Page End: 816
• Publication Date: 2013-05-28
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22076
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>To obtain a landscape of gross genetic alterations in small cell lung cancer (SCLC), genome‐wide copy number analysis and whole‐transcriptome sequencing were performed in 58 and 42 SCLCs, respectively. Focal amplification of known oncogene loci, <italic>MYCL1</italic> (1p34.2), <italic>MYCN</italic> (2p24.3), and <italic>MYC</italic> (8q24.21), was frequently and mutually exclusively detected. <italic>MYCL1</italic> and <italic>MYC</italic> were co‐amplified with other regions on either the same or the different chromosome in several cases. In addition, the 9p24.1 region was identified as being amplified in SCLCs without amplification of <italic>MYC</italic> family oncogenes. Notably, expression of the <italic>KIAA1432</italic> gene in this region was significantly higher in <italic>KIAA1432</italic> amplified cells than in non‐amplified cells, and its mRNA expression showed strong correlations with the copy numbers. Thus, <italic>KIAA1432</italic> is a novel gene activated by amplification in SCLCs. By whole‐transcriptome sequencing, a total of 60 fusion transcripts, transcribed from 95 different genes, were identified as being expressed in SCLC cells. However, no in‐frame fusion transcripts were recurrently detected in ≥2 SCLCs, and genes in the amplified regions, such as <italic>PVT1</italic> neighboring <italic>MYC</italic> and <italic>RLF</italic> in <italic>MYCL1</italic> amplicons, were recurrently fused with genes in the same amplicons or with those in different amplicons on either the same or different chromosome. Thus, it was indicated that amplification and fusion of several genes on chromosomes 1 and 8 occur simultaneously but not sequentially through chromothripsis in the development of SCLC, and amplification rather than fusion of genes plays an important role in its development. © 2013 Wiley Periodicals, Inc.</p> </abstract>