PMID- 29455316
OWN - NLM
STAT- MEDLINE
DCOM- 20180927
LR  - 20181113
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 45
IP  - 3
DP  - 2018 Jun
TI  - Investigation of major genetic alterations in neuroblastoma.
PG  - 287-295
LID - 10.1007/s11033-018-4161-4 [doi]
AB  - Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. This 
      malignancy shows a wide spectrum of clinical outcome and its prognosis is 
      conditioned by manifold biological and genetic factors. We investigated the tumor 
      genetic profile and clinical data of 29 patients with NB by multiplex 
      ligation-dependent probe amplification (MLPA) to assess therapeutic risk. In 18 
      of these tumors, MYCN status was assessed by fluorescence in situ hybridization 
      (FISH). Copy number variation was also determined for confirming MLPA findings in 
      two 6p loci. We found 2p, 7q and 17q gains, and 1p and 11q losses as the most 
      frequent chromosome alterations in this cohort. FISH confirmed all cases of MYCN 
      amplification detected by MLPA. In view of unexpected 6p imbalance, copy number 
      variation of two 6p loci was assessed for validating MLPA findings. Based on 
      clinical data and genetic profiles, patients were stratified in pretreatment risk 
      groups according to international consensus. MLPA proved to be effective for 
      detecting multiple genetic alterations in all chromosome regions as requested by 
      the International Neuroblastoma Risk Group (INRG) for therapeutic stratification. 
      Moreover, this technique proved to be cost effective, reliable, only requiring 
      standard PCR equipment, and attractive for routine analysis. However, the 
      observed 6p imbalances made PKHD1 and DCDC2 inadequate for control loci. This 
      must be considered when designing commercial MLPA kits for NB. Finally, four 
      patients showed a normal MLPA profile, suggesting that NB might have a more 
      complex genetic pattern than the one assessed by presently available MLPA kits.
FAU - Costa, Regis Afonso
AU  - Costa RA
AD  - Genetics Program, Instituto Nacional de Cancer, Rua Andre Cavalcanti 37, Rio de 
      Janeiro, RJ, 20231-050, Brazil.
AD  - Department of Genetics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      Brazil.
FAU - Seuanez, Hector N
AU  - Seuanez HN
AUID- ORCID: 0000-0003-3355-8003
AD  - Genetics Program, Instituto Nacional de Cancer, Rua Andre Cavalcanti 37, Rio de 
      Janeiro, RJ, 20231-050, Brazil. hseuanez@inca.gov.br.
AD  - Department of Genetics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      Brazil. hseuanez@inca.gov.br.
LA  - eng
GR  - 573806/2008-0/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Journal Article
DEP - 20180217
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
SB  - IM
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Aberrations
MH  - Cohort Studies
MH  - DNA Copy Number Variations
MH  - Female
MH  - Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Infant
MH  - Male
MH  - Multiplex Polymerase Chain Reaction/methods
MH  - Mutation
MH  - Neuroblastoma/*genetics
MH  - Prognosis
OTO - NOTNLM
OT  - Chromosome 6
OT  - Genetic alterations
OT  - MLPA
OT  - MYCN
OT  - Neuroblastoma
EDAT- 2018/02/20 06:00
MHDA- 2018/09/28 06:00
CRDT- 2018/02/19 06:00
PHST- 2017/10/04 00:00 [received]
PHST- 2018/02/08 00:00 [accepted]
PHST- 2018/02/20 06:00 [pubmed]
PHST- 2018/09/28 06:00 [medline]
PHST- 2018/02/19 06:00 [entrez]
AID - 10.1007/s11033-018-4161-4 [pii]
AID - 10.1007/s11033-018-4161-4 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2018 Jun;45(3):287-295. doi: 10.1007/s11033-018-4161-4. Epub 2018 
      Feb 17.