Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis

Kumiko Uryu, Riki Nishimura, Keisuke Kataoka, Yusuke Sato, Atsuko Nakazawa, Hiromichi Suzuki, Kenichi Yoshida, Masafumi Seki, Mitsuteru Hiwatari, Tomoya Isobe, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Katsuyoshi Koh, Ryoji Hanada, Akira Oka, Yasuhide Hayashi, Miki Ohira, Takehiko KamijoHiroki Nagase, Tetsuya Takimoto, Tatsuro Tajiri, Akira Nakagawara, Seishi Ogawa, Junko Takita

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeteddeep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated using immunohistochemical analysis in 259 samples. Based on genetic alterations, the following 6 subgroups were identified: groups A (ALK abnormalities), B (other gene mutations), C (MYCN amplification), D (11q loss of heterozygosity [LOH]), E (at least 1 copy number variants), and F (no genetic changes). Groups A to D showed advanced disease and poor prognosis, whereas groups E and F showed excellent prognosis. Intriguingly, in group A, MYCN amplification was not a significant prognostic marker, while high ALK expression was a relevant indicator for prognosis (P = 0.033). Notably, the co-existence of MYCN amplification and 1p LOH, and the co-deletion of 3p and 11q were significant predictors of relapse (P = 0.043 and P = 0.040). Additionally, 6q/8p LOH and 17q gain were promising indicators of survival in patients older than 5 years, and 1p, 4p, and 11q LOH potentially contributed to outcome prediction in the intermediate-risk group. Our genetic overview clarifies the clinical impact of genetic signatures and aids in the better understanding of genetic basis of neuroblastoma.

Original languageEnglish
Pages (from-to)107513-107529
Number of pages17
JournalOncotarget
Volume8
Issue number64
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • ALK
  • ALK immunohistochemistry staining
  • Copy number variants
  • Japan neuroblastoma study group (JNBSG)
  • Target amplicon deep sequencing

ASJC Scopus subject areas

  • Oncology

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