Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes

Area of Science:

• Genomics and Oncology
• Neuro-oncology
• Cancer Biology

Background:

• Choroid plexus carcinomas (CPCs) represent a significant challenge due to their poor understanding and limited therapeutic strategies.
• Identifying the genetic drivers of CPC is critical for developing effective treatments.

Purpose of the Study:

• To conduct a genome-wide search for oncogenes involved in CPC development across species.
• To identify genes located in amplified chromosomal regions in both human and mouse CPC models.

Main Methods:

• Utilized a mouse model of choroid plexus carcinoma alongside a large cohort of human CPC samples.
• Performed cross-species, genome-wide analysis focusing on syntenic regions of chromosome gain.
• Investigated the functional requirement of identified oncogenes in disease initiation and progression.

Main Results:

• Identified TAF12, NFYC, and RAD54L as concurrently gained oncogenes in CPC tumors from both species.
• These genes are located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3.
• TAF12 and NFYC function as transcription factors regulating the epigenome, while RAD54L is involved in DNA repair.

Conclusions:

• The concurrent gain and cooperative function of TAF12, NFYC, and RAD54L are essential for CPC formation.
• These findings highlight potential therapeutic targets for treating choroid plexus carcinomas.
• This study provides novel insights into the molecular mechanisms driving CPC tumorigenesis.