Genomic profiling of a metastatic anaplastic melanocytic neuroectodermal tumor arising from a mature thymic teratoma as part of a mediastinal germ cell tumor.

Fiche publication

Date publication

avril 2023

Journal

Cold Spring Harbor molecular case studies

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak , Pr KURTZ Jean-Emmanuel , Dr CARAPITO Raphaël , Dr LHERMITTE Benoît , Dr GANTZER Justine

Tous les auteurs :
Mayeur S, Lhermitte B, Gantzer J, Molitor A, Stemmelen T, Meyer S, Kolmer A, Kurtz JE, Bahram S, Carapito R

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/37160315

Résumé

Following chemotherapy, a mediastinal germ cell tumor can lead to a mature teratoma that is composed of tissues derived from all three germ layers. Although teratoma is usually curable, in rare cases it can give rise to various somatic tumors and exceptionally it undergoes melanocytic neuroectodermal tumor (MNT) transformation, a process that is not well-described. We report a patient with a postchemotherapy thymic teratoma associated with an MNT component who, 10 years later, additionally presented a vertebral metastasis corresponding to an anaplastic MNT. Using exome sequencing of the mature teratoma, the MNT and its metastatic vertebral anaplastic MNT components, we identified 19 somatic mutations shared by at least two components. Six mutations were common to all three components, and three of them were located in the known cancer-related genes (p.E63K), (p.P222X), and (p.S447P). Gene set enrichment analysis revealed that the melanoma tumorigenesis pathway was enriched in mutated genes including the four major driver genes , , , and , indicating that these genes may be involved in the development of the anaplastic MNT transformation of the teratoma. To our knowledge, this is the first molecular study realized on MNT. Understanding the clinicopathological and molecular characteristics of these tumors is essential to better understand their development and to improve therapeutics.