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  3. Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.

Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Hartley HE
  • Fong FC
  • Gabriel AS
  • Stevenson LK
  • Beckett E
  • Allinson LM
  • Goodman A
  • Potts A
  • Whittle E
  • Barford R
  • Lamparelli A
  • Herd F
  • Mazzocco K
  • Pezzolo A
  • Morini M
  • Ardito M
  • Eva A
  • Ognibene M
  • Fischer M
  • Ackermann S
  • Rosswog C
  • Hero B
  • Smith GR
  • Unsworth AA
  • McCorkindale M
  • George SL
  • Tall J
  • Molenaar JJ
  • Matser Y
  • Langenberg K
  • Tytgat G
  • Noguera R
  • Berbegall AP
  • Combaret V
  • Pierron G
  • Mühlethaler-Mottet A
  • Schoumans J
  • Tchinda J
  • Banzola I
  • Jeison M
  • Hameiri-Grossman M
  • Beiske KH
  • Auger N
  • Van Roy N
  • Basta NO
  • McNally RJQ
  • Taschner-Mandl S
  • Papadakis V
  • Di Cataldo A
  • Wheeler K
  • Bermúdez JD
  • Beck-Popovic M
  • Canete A
  • Schleiermacher G
  • Tweddle DA

Grupos

Abstract

PURPOSE: Intermediate-risk neuroblastoma patients older than 18 months, with non-MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup. METHODS: We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival. RESULTS: Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS. CONCLUSION: Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.

Datos de la publicación

ISSN/ISSNe:
2473-4284, 2473-4284

JCO Precision Oncology  LIPPINCOTT WILLIAMS & WILKINS

Tipo:
Article
Páginas:
-
PubMed:
42385103
Factor de Impacto:
2,116 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 1

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