Comparative genetic study of intratumoral heterogenous XXXX amplified @entity521 versus aggressive genetic profile neuroblastic tumors.

@entity5 @entity1 @entity4180 @entity521
Intratumoral heterogeneous @entity4180 amplification (hetMNA) is an unusual event in @entity521 with unascertained biological and clinical implications. Diagnosis is based on the detection of @entity4180 amplification surrounded by non-amplified @entity5 cells by fluorescence in situ hybridization (FISH). To better define the genetic features of hetMNA @entity5 , we studied the Spanish cohort of @entity5 by FISH and single nucleotide polymorphism arrays. We compared hetMNA @entity5 with homogeneous MNA (homMNA) and nonMNA @entity5 with 11q deletion (nonMNA w11q-). Of 1091 @entity5 , 28 were hetMNA by FISH. Intratumoral heterogeneity of 1p, 2p, 11q and 17q was closely associated with hetMNA @entity5 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- @entity5 . 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 @entity5 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 @entity1 .
