Expression profiling and characterization of 4200 genes cloned from primary neuroblastomas: identification of 305 genes differentially expressed between favorable and unfavorable subsets

• Published in: Oncogene Vol. 22; no. 35; pp. 5525 - 5536
• Main Authors: OHIRA, Miki, MOROHASHI, Aiko, SUZUKI, Yutaka, SUGANO, Sumio, GOTO, Takeshi, SATO, Shuji, NAKAGAWARA, Akira, INUZUKA, Hiroyuki, SHISHIKURA, Tomotane, KAWAMOTO, Takemasa, KAGEYAMA, Hajime, NAKAMURA, Yohko, ISOGAI, Eriko, TAKAYASU, Hajime, SAKIYAMA, Shigeru
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 21.08.2003; Nature Publishing Group
• Subjects: Biological and medical sciences; Biology; Cancer; Catecholamines; Cell death; Cell differentiation; Children; Chromosome Mapping; Cloning; Complementary DNA; DNA, Complementary; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Library; Gene mapping; Genes. Genome; Humans; Medical prognosis; Medical sciences; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Neural crest; Neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neurology; RNA-directed DNA polymerase; Sequence Analysis, DNA; Solid tumors; Synaptogenesis; Transcription factors; TrkA protein; TrkA receptors; Tumorigenesis; Tumors; Tumors of the nervous system. Phacomatoses; Japan; Nervous system diseases; Capping; Regression; Identification; Malignant tumor; Neuroblastoma; Characterization; MYCN; Gene; Library; oligo- capping cDNA library; Autonomic neuropathy; Differentiation; expression profile
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1206853

Neuroblastoma (NBL), one of the most common childhood solid tumors, has a distinct nature in different prognostic subgroups: NBL in patients under 1 year of age usually regresses spontaneously, whereas that in patients over 1 year of age often grows aggressively and eventually kills the patient. To understand the molecular mechanism of biology and tumorigenesis of NBL, we decided to perform a comprehensive approach to unveil the gene expression profiles among the NBL subsets. We constructed the subset-specific oligo-capping cDNA libraries from the primary NBL tissues with favorable (F: stage 1, high expression of TrkA and a single copy of MYCN) and unfavorable (UF: stage 3 or 4, decreased expression of TrkA and MYCN amplification) characteristics and randomly cloned 4654 cDNAs. Among 4243 cDNAs sequenced successfully, 1799 (42.4%) were the genes with unknown function. Excluding the housekeeping genes, an expression profile of each subset was extremely different. To determine the genes expressed differentially between F and UF subsets, we performed semiquantitative reverse transcriptase (RT)-PCR for each of the 1842 independent genes using RNA obtained from 16 F and 16 UF NBLs as template. This revealed that 278 genes were highly expressed in the F subset as compared to the UF one, while, surprisingly, only 27 genes were expressed at higher levels in the UF rather than the F subset. These differentially expressed genes included 194 genes with unknown function. Many of the genes expressed at high levels in the F subset were related to catecholamine biosynthesis, small GTPases, synapse formation, synaptic vesicle transport, and transcription factors regulating differentiation of the neural crest-derived cells. On the other hand, the genes expressed at high levels in the UF subset included transcription factors and/or receptors that might regulate neuronal growth and differentiation. The chromosomal mapping of those genes showed some clusters. Thus, our mass-identification and characterization of the differentially expressed genes between the subsets may become a powerful tool for finding the important genes of NBL as well as developing new diagnostic and therapeutic strategies against aggressive NBL.