Role of chromosome 9p21.3 loss in anaplastic thyroid cancer transformation

• Applicant: Dr. Julia Maier
• Subject Area: Hematology, Oncology ; General Genetics and Functional Genome Biology ; Cell Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576570573

Anaplastic thyroid cancers (ATC) are one of the most aggressive tumors overall, with patients showing a median survival rate of only six months. ATCs can evolve from pre-existing papillary thyroid cancers (PTC), via the acquisition of specific genetic alterations. Our laboratory aims at understanding which mechanisms are switched on and off in cells that undergo ATC transformation, to ultimately design better treatments. Most genetic alterations in cancer are point mutations, that is, changes in the sequence of letters of the DNA. Here, we will study a different type of defects known as copy number alterations (CNA). CNAs do not involve a change in the gene alphabet, but instead, a changed gene dosage. We will focus on a large CNA affecting chromosome 9, known as chr9p21del, whose consequence is the complete loss of a series of genes. Chr9p21del is the most frequent CNA in multiple cancer types, and it is enriched in the highly aggressive ATCs vs. the mostly indolent PTCs (40% vs. 2%, respectively). We will use a technology based on CRISPR gene editing that a collaborator of this project will provide to generate mouse models of ATC with chr9p21del. We detail plans to assess the specific contributions of each of the genes contained in this genomic region. We will evaluate their role in cell growth, metastatic dissemination and infiltration of tumors by immune cells. We will employ these models to assess combinations of various inhibitors for their ability to block ATC growth. We will then employ materials from ATC tumors from patients at Gustave Roussy to validate our observations, with the ultimate goal of unveiling potential targets for refined therapeutic strategies.

• DFG Programme: WBP Fellowship
• International Connection: France
• Host: Professor Iñigo Landa, Ph.D.