PMID- 29390274
OWN - NLM
STAT- MEDLINE
DCOM- 20180212
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 96
IP  - 50
DP  - 2017 Dec
TI  - A highly malignant case of neuroblastoma with substantial increase of 
      single-nucleotide variants and normal mismatch repair system: A case report.
PG  - e8845
LID - 10.1097/MD.0000000000008845 [doi]
LID - e8845
AB  - RATIONALE: Neuroblastoma is a common abdominal malignancy in children. The 
      chemoresistant and relapsed cases have poor prognosis. The genetic background and 
      the mechanism of resistance remain unelucidated. Next-generation sequence (NGS) 
      is becoming a popular tool to unravel the genetic background and to guide 
      precision medicine in oncology studies as well as in clinical practice. PATIENT 
      CONCERNS: Here we report a neuroblastoma case of a boy aged 2 years and 8 months 
      when first diagnosed, with multiple metastatic sites found in both lungs. The 
      metastatic tumors were resistant to chemotherapy and the patient suffered from 
      severe bone marrow suppression. NGS of the whole exon revealed somatic mutations 
      including 9666 single-nucleotide variants (SNVs) from 5148 genes, 55 copy number 
      variations (CNVs), and 140 insertion-deletion variations. The high frequency of 
      SNVs makes it distinguished case. However, no mutation of key tumor driver genes 
      with functional significance was identified. No abnormality was found in nucleic 
      acid synthesis enzymes. No amplification of c-Myc and n-Myc was found by 
      fluorescence in situ hybridization (FISH). Both NGS and immunohistochemistry 
      (IHC) analysis indicated that DNA mismatch repair (MMR) system was intact. 
      INTERVENTIONS: After initial diagnosis, the patient received combinational 
      chemotherapy, which includes vindesine, an analogue of adriamycin suggested by 
      NGS data, for 4 months. Radical section of the tumor together with the left 
      kidney and the left adrenal gland was performed 5 months after diagnosis. 
      Postsurgical chemotherapy protocols was similar with the previous. OUTCOMES: The 
      patient died 2 years after initial diagnosis after 8 relapses following 
      combinational chemotherapy. LESSONS: This case of neuroblastoma is with 
      pronounced somatic mutations but unidentified driver gene and therapeutic target. 
      Although NGS is a potentially powerful tool to guide precision medicine, at 
      current stage, its application in the clinic certainly has its limits. The 
      underlying mechanism of the substantially increased SNV number, as well as the 
      malignant behaviors of the tumor, is yet to be revealed.
CI  - Copyright (c) 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights 
      reserved.
FAU - Yuan, Lin-Qing
AU  - Yuan LQ
AD  - Departments of Central Laboratory, Pathology, Oncology and Radiology, The 
      Children's Hospital of Zhejiang University School of Medicine Institute of 
      Translational Medicine, Zhejiang University The Key Laboratory of Diagnosis and 
      Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.
FAU - Wang, Jin-Hu
AU  - Wang JH
FAU - Zhu, Kun
AU  - Zhu K
FAU - Yang, Min
AU  - Yang M
FAU - Gu, Wei-Zhong
AU  - Gu WZ
FAU - Lai, Can
AU  - Lai C
FAU - Li, Hao-Min
AU  - Li HM
FAU - Shu, Qiang
AU  - Shu Q
FAU - Chen, Xi
AU  - Chen X
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
SB  - IM
MH  - *Abdomen
MH  - Child, Preschool
MH  - *DNA Copy Number Variations
MH  - *DNA Mismatch Repair
MH  - Fatal Outcome
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mutation
MH  - Neuroblastoma/*genetics/*pathology
MH  - *Polymorphism, Single Nucleotide
PMC - PMC5815686
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2018/02/03 06:00
MHDA- 2018/02/13 06:00
PMCR- 2017/12/15
CRDT- 2018/02/03 06:00
PHST- 2018/02/03 06:00 [entrez]
PHST- 2018/02/03 06:00 [pubmed]
PHST- 2018/02/13 06:00 [medline]
PHST- 2017/12/15 00:00 [pmc-release]
AID - 00005792-201712150-00024 [pii]
AID - MD-D-17-05245 [pii]
AID - 10.1097/MD.0000000000008845 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2017 Dec;96(50):e8845. doi: 10.1097/MD.0000000000008845.