Comparative genetic study of intratumoral heterogenous MYCN amplified neuroblastoma versus aggressive genetic profile neuroblastic tumors

Data de publicació: 17/03/2016

Autors de IIS La Fe

Adela Cañete Nieto

Autor
Victoria Castel Sánchez

Autor

Autors aliens a IIS La Fe

Berbegall, AP
Villamon, E
Piqueras, M
Tadeo, I
Djos, A
Ambros, PF
Martinsson, T
Ambros, IM
Navarro, S
Noguera, R

Grups d'Investigació

Investigación Clínica y Traslacional en Cáncer

Leader

José Gómez Codina

Abstract

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.

Dades de la publicació

ISSN/ISSNe:: 0950-9232, 1476-5594
Tipus:: Article
Pàgines:: 1423-1432
DOI:: 10.1038/onc.2015.200
PubMed:: 26119945
Factor d'Impacte:: 3,436 SCImago ℠
Quartil:: Q1 SCImago ℠

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Mètriques

Filiacions

Berbegall, AP:: Univ Valencia, Med Res Fdn, INCLIVA, Pathol Dept,Med Sch, Valencia, Spain
Villamon, E:: Univ Valencia, Med Res Fdn, INCLIVA, Pathol Dept,Med Sch, Valencia, Spain
Piqueras, M:: Univ Valencia, Med Res Fdn, INCLIVA, Pathol Dept,Med Sch, Valencia, Spain
Tadeo, I:: Univ Valencia, Med Res Fdn, INCLIVA, Pathol Dept,Med Sch, Valencia, Spain
Djos, A:: Univ Gothenburg, Sahlgrenska Acad, Dept Med & Clin Genet, Gothenburg, Sweden
Ambros, PF:: St Anna Kinderkrebsforschung, Childrens Canc Res Inst, Vienna, Austria

Hosp Univ & Politecn La Fe, Pediat Oncol Unit, Valencia, Spain
Martinsson, T:: Univ Gothenburg, Sahlgrenska Acad, Dept Med & Clin Genet, Gothenburg, Sweden
Ambros, IM:: St Anna Kinderkrebsforschung, Childrens Canc Res Inst, Vienna, Austria
Canete, A:: Hosp Univ & Politecn La Fe, Pediat Oncol Unit, Valencia, Spain
Castel, V:: Hosp Univ & Politecn La Fe, Pediat Oncol Unit, Valencia, Spain
Navarro, S:: Univ Valencia, Med Res Fdn, INCLIVA, Pathol Dept,Med Sch, Valencia, Spain
Noguera, R:: Univ Valencia, Med Res Fdn, INCLIVA, Pathol Dept,Med Sch, Valencia, Spain