Typical numerical alterations in genome identified by array CGH analysis in neuroblastoma tumors

Katarzyna Szewczyk; Katarzyna Szewczyk

doi:10.3934/molsci.2021019

AIMS Molecular Science

2021, Volume 8, Issue 4: 248-256. doi: 10.3934/molsci.2021019

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Research article

Typical numerical alterations in genome identified by array CGH analysis in neuroblastoma tumors

Katarzyna Szewczyk ^{1,2
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1.
Department of Medical Genetics, Faculty of Medicine, Jagiellonian University Medical College, Poland
2.
Department of Medical Genetics, University Children's Hospital of Krakow, Wielicka St. 265, 30-663 Krakow, Poland

Received: 14 September 2021 Accepted: 22 November 2021 Published: 26 November 2021

Introduction
The clinical variability in the course of neuroblastoma (NB) is closely linked to diverse genetic changes acquired by tumor cells. Rapid NB progression is associated with oncogene MYCN amplification (MNA) and segmental chromosomal aberrations (SCA). Alternatively, numerical chromosomal alterations (NCA) have positive impact on treatment. So far, no studies have been undertaken to identify NCA that may group NB patients. Therefore, the aim of the study was to identify NCA typical for NB.

Materials and methods
Copy number alterations in NB tumor genome (fresh samples N = 94; formalin-fixed paraffin-embedded specimens N = 66) were analyzed with a pangenomic array CGH technique.

Results
The profile with NCA was observed in 72 (45%) cases, NCA+SCA in 37 (23%), normal in 35 (22%) and MNA in 16 (10%). Samples with NCA were characterized by whole chromosome gains: 17, 7, 6 (78%, 65%, 51%, respectively) and copy loss of chromosome 14 (57%). Similarly to NCA, patients with a combined NCA and SCA profile were also characterized by gain of whole chromosome 17 and 7 (35% both) and loss of chromosome 14 (38%), but with lower frequency. In the combined NCA and SCA profiles, typical NB changes such as deletion 1p36 (27%) and gain 17q (41%) were observed, as well as deletion 11q (24%). The same alterations were detected in MNA samples (44%, 44%, 19%, respectively). A difference was found in spanning 11q deletion between MNA and NCA+SCA subgroup, which may suggest new prognostic markers in NB. In MNA subgroup specific NCA was not indicated.

Conclusions
The hypothesis that NCA in NB tumors are more frequent in younger children with good prognosis was confirmed. To gain new insights into the pathogenesis of NB and to establish molecular targets for diagnosis and therapy, candidate genes in the altered chromosomal regions must be investigated.
- neuroblastoma,
- numerical chromosomal alteration,
- structural chromosomal alteration
Citation: Katarzyna Szewczyk. Typical numerical alterations in genome identified by array CGH analysis in neuroblastoma tumors[J]. AIMS Molecular Science, 2021, 8(4): 248-256. doi: 10.3934/molsci.2021019

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Abstract

Introduction

The clinical variability in the course of neuroblastoma (NB) is closely linked to diverse genetic changes acquired by tumor cells. Rapid NB progression is associated with oncogene MYCN amplification (MNA) and segmental chromosomal aberrations (SCA). Alternatively, numerical chromosomal alterations (NCA) have positive impact on treatment. So far, no studies have been undertaken to identify NCA that may group NB patients. Therefore, the aim of the study was to identify NCA typical for NB.

Materials and methods

Copy number alterations in NB tumor genome (fresh samples N = 94; formalin-fixed paraffin-embedded specimens N = 66) were analyzed with a pangenomic array CGH technique.

Results

The profile with NCA was observed in 72 (45%) cases, NCA+SCA in 37 (23%), normal in 35 (22%) and MNA in 16 (10%). Samples with NCA were characterized by whole chromosome gains: 17, 7, 6 (78%, 65%, 51%, respectively) and copy loss of chromosome 14 (57%). Similarly to NCA, patients with a combined NCA and SCA profile were also characterized by gain of whole chromosome 17 and 7 (35% both) and loss of chromosome 14 (38%), but with lower frequency. In the combined NCA and SCA profiles, typical NB changes such as deletion 1p36 (27%) and gain 17q (41%) were observed, as well as deletion 11q (24%). The same alterations were detected in MNA samples (44%, 44%, 19%, respectively). A difference was found in spanning 11q deletion between MNA and NCA+SCA subgroup, which may suggest new prognostic markers in NB. In MNA subgroup specific NCA was not indicated.

Conclusions

The hypothesis that NCA in NB tumors are more frequent in younger children with good prognosis was confirmed. To gain new insights into the pathogenesis of NB and to establish molecular targets for diagnosis and therapy, candidate genes in the altered chromosomal regions must be investigated.

Acknowledgments

I would like to thank the pediatric oncologists and geneticists in Poland who strive to increase knowledge about neuroblastoma pathogenesis.

Conflict of interest

The author declares no conflict of interest in this paper.

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