Duplication of ALK F1245 missense mutation due to acquired uniparental disomy associated with aggressive progression in a patient with relapsed neuroblastoma.

ABSTRACT: Recent genome-wide analysis of neuroblastoma (NBL) revealed amplification and heterozygous mutation of anaplastic lymphoma kinase (ALK) are responsible for oncogenicity, frequently observed during relapses. A 3-year-old girl with relapsed high-risk NBL had a heterozygous ALK F1245L mutation at diagnosis, which became homozygous due to uniparental disomy (UPD) of the entire chromosome 2, confirmed by single nucleotide polymorphism array and variant allele frequency of this mutation. The ALK inhibitor, crizotinib, failed to control the tumor and the patient died of the disease. Further genomic analysis using targeted capture sequencing for 381 genes related to pediatric cancers identified more alterations acquired at relapse, such as TSC complex subunit 2 and protein tyrosine p

SUBMITTER: Kimura S 

PROVIDER: S-EPMC6396392 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature