title: Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer.
abstract: 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, MYCL1 (1p34.2), MYCN (2p24.3), and MYC (8q24.21), was frequently and mutually exclusively detected. MYCL1 and MYC 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 MYC family oncogenes. Notably, expression of the KIAA1432 gene in this region was significantly higher in KIAA1432 amplified cells than in non-amplified cells, and its mRNA expression showed strong correlations with the copy numbers. Thus, KIAA1432 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 PVT1 neighboring MYC and RLF in MYCL1 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.
authors.affiliation: Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Takenaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Totoki
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Aiko
authors.initials: A
authors.lastname: Sato-Otsubo
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005784:Gene Amplification; D018628:Gene Dosage; D050939:Gene Fusion; D016259:Genes, myc; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000235:genetics*; D059467:Transcriptome; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C505231:RIC1 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2