Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Oncotarget, 2017-12, Vol.8 (64), p.107513-107529

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep 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 ( abnormalities), B (other gene mutations), C ( 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, amplification was not a significant prognostic marker, while high ALK expression was a relevant indicator for prognosis ( = 0.033). Notably, the co-existence of amplification and 1p LOH, and the co-deletion of 3p and 11q were significant predictors of relapse ( = 0.043 and = 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.