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. 2023 Oct;483(4):477-486.
doi: 10.1007/s00428-023-03604-8. Epub 2023 Jul 17.

MYCN amplification, TERT rearrangements and ATRX mutations in neuroblastoma: clinicopathological correlates- an Indian perspective

Aadya N Kerkar  1 , Dheeraj Chinnam  2 , Aanchal Verma  3 , Nitin J Peters  4 , Nandita Kakkar  3 , Amita Trehan  5 , Minu Singh  5 , Kirti Gupta  6
Affiliations

MYCN amplification, TERT rearrangements and ATRX mutations in neuroblastoma: clinicopathological correlates- an Indian perspective

Aadya N Kerkar et al. Virchows Arch. 2023 Oct.

Abstract

Background: Neuroblastoma (NB) is the most common extracranial solid tumour in childhood with a diverse clinical presentation and course. The early age of onset, high frequency of metastatic disease at diagnosis and tendency for spontaneous regression in infancy sets it apart from other childhood tumors. This heterogeneity is largely attributed to underlying genetic aberrations which are distinct in low-risk and high-risk NB. To this end, we sought to analyse our NB cases for the molecular alterations and find its correlation with clinical behaviour.

Methods: NB cases (n = 50) diagnosed over last 7 years were retrospectively analysed for MYCN amplification (fluorescent-in-situ hybridization), TERT rearrangements (qRT-PCR), ATRX mutations (immunohistochemistry). These findings were correlated with demographic profiles, histologic features and clinical outcome.

Results: Age ranged from 1 month to 30 years (mean 2.8 years) with male preponderance. Poorly differentiated subtype constituted the majority (64%), followed by differentiating (28%) and undifferentiated subtype (8%) which were equally distributed across all age groups. MYCN amplification, TERT-mRNA upregulation and ATRX mutations was observed in 30%, 42% and 24%, respectively. Cases with TERT-mRNA upregulation were distributed equally across all histological subtypes while those with ATRX mutations and MYCN amplification were frequent in poorly differentiated NB. ATRX mutation was mutually exclusive of TERT-mRNA upregulation and MYCN amplification. Kaplan-Meier analysis revealed significantly shorter overall and progression-free survival for tumors harboring MYCN amplification and TERT-mRNA upregulation, while that for ATRX mutant tumors was not significant.

Conclusions: Our results provide data indicating poor clinical outcome in NB carrying MYCN amplification and TERT-mRNA upregulation.

Keywords: ATRX mutation; MYCN amplification; Molecular alterations; Neuroblastoma; TERT rearrangements.

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