Whole genome profiling of primary and metastatic adrenocortical carcinoma unravels significant molecular events. Academic Article uri icon

Overview

abstract

  • Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with limited treatment options and poor prognosis, with a 5-year survival rate of about 15 %. This study used whole genome sequencing to characterize the genomic landscape of five patients, one of them with both primary and metastatic samples. Key driver mutations were detected, including APC, JAK1, RFWD3 as well as other genes. Notably, a primary tumor harbored a RAD51 biallelic deleterious translocation, associated with homologous recombination deficiency signature. Large-scale copy neutral loss of heterozygosity (LOH) was identified in four tumors, three had TP53 mutations, with structural variants impacting genes as RB1, CDKN2A, and NF1. A genomic signature specific to mismatch repair was observed in a sample with MHS6 mutation. Two tumors presented novel fusions at TERT locus, including TERT::ZNF521. Comparative analysis between conventional and oncocytic ACC subtypes revealed no significant differences in mutation load, microsatellite instability, or specific gene enrichment. This comprehensive WGS analysis broadens the spectrum of genomic alterations in ACC, highlighting potential molecular targets and differences across subtypes that may inform future therapeutic strategies.

publication date

  • November 29, 2024

Research

keywords

  • Adrenal Cortex Neoplasms
  • Adrenocortical Carcinoma

Identity

Digital Object Identifier (DOI)

  • 10.1016/j.prp.2024.155725

PubMed ID

  • 39626581

Additional Document Info

volume

  • 266