PMID- 26119945
OWN - NLM
STAT- MEDLINE
DCOM- 20160815
LR  - 20181113
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 35
IP  - 11
DP  - 2016 Mar 17
TI  - Comparative genetic study of intratumoral heterogenous MYCN amplified 
      neuroblastoma versus aggressive genetic profile neuroblastic tumors.
PG  - 1423-32
LID - 10.1038/onc.2015.200 [doi]
AB  - Intratumoral heterogeneous MYCN amplification (hetMNA) is an unusual event in 
      neuroblastoma with unascertained biological and clinical implications. Diagnosis 
      is based on the detection of MYCN amplification surrounded by non-amplified tumor 
      cells by fluorescence in situ hybridization (FISH). To better define the genetic 
      features of hetMNA tumors, we studied the Spanish cohort of neuroblastic tumors 
      by FISH and single nucleotide polymorphism arrays. We compared hetMNA tumors with 
      homogeneous MNA (homMNA) and nonMNA tumors with 11q deletion (nonMNA w11q-). Of 
      1091 primary tumors, 28 were hetMNA by FISH. Intratumoral heterogeneity of 1p, 
      2p, 11q and 17q was closely associated with hetMNA tumors when analyzing 
      different pieces for each case. For chromosome 2, 16 cases showed 2p intact, 4 
      focal gain at 2p24.3 and 8 MNA. The lengths of the smallest regions of overlap 
      (SROs) for 2p gains and 1p deletions were between the SRO lengths observed in 
      homMNA and nonMNA w11q- tumors. Co-occurrence of 11q- and +17q was frequently 
      found with the largest SROs for both aberrations. The evidence for and frequency 
      of different genetic subpopulations representing a hallmark of the hetMNA 
      subgroup of NB indicates, on one hand, the presence of a considerable genetic 
      instability with different SRO of either gains and losses compared with those of 
      the other NB groups and highlights and, on the other hand, the need for multiple 
      sampling from distant and macroscopically and microscopically distinct tumor 
      areas. Narrowing down the different SRO for both deletions and gains in NB groups 
      would be crucial to pinpointing the candidate gene(s) and the critical gene 
      dosage with prognostic and therapeutic significance. This complexity of segmental 
      chromosomal aberration patterns reinforces the necessity for a larger cohort 
      study using FISH and pangenomic techniques to develop a suitable therapeutic 
      strategy for these patients.
FAU - Berbegall, A P
AU  - Berbegall AP
AD  - Pathology Department, Medical School, University of Valencia, Medical Research 
      Foundation, INCLIVA, Valencia, Spain.
FAU - Villamon, E
AU  - Villamon E
AD  - Pathology Department, Medical School, University of Valencia, Medical Research 
      Foundation, INCLIVA, Valencia, Spain.
FAU - Piqueras, M
AU  - Piqueras M
AD  - Pathology Department, Medical School, University of Valencia, Medical Research 
      Foundation, INCLIVA, Valencia, Spain.
FAU - Tadeo, I
AU  - Tadeo I
AD  - Pathology Department, Medical School, University of Valencia, Medical Research 
      Foundation, INCLIVA, Valencia, Spain.
FAU - Djos, A
AU  - Djos A
AD  - Department of Medical and Clinical Genetics, Sahlgrenska Academy at the 
      University of Gothenburg, Gothenburg, Sweden.
FAU - Ambros, P F
AU  - Ambros PF
AD  - CCRI, Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, 
      Austria.
AD  - Pediatric Oncology Unit, Hospital Universitario y Politecnico La Fe, Valencia, 
      Spain.
FAU - Martinsson, T
AU  - Martinsson T
AD  - Department of Medical and Clinical Genetics, Sahlgrenska Academy at the 
      University of Gothenburg, Gothenburg, Sweden.
FAU - Ambros, I M
AU  - Ambros IM
AD  - CCRI, Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, 
      Austria.
FAU - Canete, A
AU  - Canete A
AD  - Pediatric Oncology Unit, Hospital Universitario y Politecnico La Fe, Valencia, 
      Spain.
FAU - Castel, V
AU  - Castel V
AD  - Pediatric Oncology Unit, Hospital Universitario y Politecnico La Fe, Valencia, 
      Spain.
FAU - Navarro, S
AU  - Navarro S
AD  - Pathology Department, Medical School, University of Valencia, Medical Research 
      Foundation, INCLIVA, Valencia, Spain.
FAU - Noguera, R
AU  - Noguera R
AD  - Pathology Department, Medical School, University of Valencia, Medical Research 
      Foundation, INCLIVA, Valencia, Spain.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150629
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (MYCN protein, human)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - Chromosome 1, monosomy 1p
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 1/genetics
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Chromosomes, Human, Pair 2/genetics
MH  - Cohort Studies
MH  - Gene Dosage/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - N-Myc Proto-Oncogene Protein
MH  - Neuroblastoma/classification/*genetics
MH  - Nuclear Proteins/*genetics
MH  - Oncogene Proteins/*genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Young Adult
EDAT- 2015/06/30 06:00
MHDA- 2016/08/16 06:00
CRDT- 2015/06/30 06:00
PHST- 2015/01/05 00:00 [received]
PHST- 2015/04/08 00:00 [revised]
PHST- 2015/05/10 00:00 [accepted]
PHST- 2015/06/30 06:00 [entrez]
PHST- 2015/06/30 06:00 [pubmed]
PHST- 2016/08/16 06:00 [medline]
AID - onc2015200 [pii]
AID - 10.1038/onc.2015.200 [doi]
PST - ppublish
SO  - Oncogene. 2016 Mar 17;35(11):1423-32. doi: 10.1038/onc.2015.200. Epub 2015 Jun 
      29.