Allelic Expression Imbalance Analysis Identified YAP1 Amplification in p53- Dependent Osteosarcoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Osteosarcoma (OS) is a primary bone cancer often linked to adolescent growth and genetic factors like TP53 mutations.
• Identifying OS driver mutations is complex due to intricate bone growth pathways and tumor heterogeneity.

Purpose of the Study:

• To investigate the molecular mechanisms driving osteosarcoma (OS) in a TP53-mutated porcine model.
• To identify key genetic alterations and pathways involved in OS development and progression.

Main Methods:

• Utilized RNA sequencing and allele expression imbalance (AEI) analysis in a porcine model of TP53-mutated OS.
• Performed copy number variation analysis to assess genetic alterations.
• Investigated the functional impact of YAP1 inactivation on OS cell behavior and gene expression.

Main Results:

• A highly significant allele expression imbalance (AEI) was observed for SNPs in the BIRC3-YAP1 locus.
• YAP1 amplification was strongly associated with OS progression and AEI.
• YAP1 inactivation suppressed proliferation, migration, and invasion, silencing TP63 and restoring p16 expression in p53-deficient OS cells.

Conclusions:

• YAP1 amplification plays a critical role in the progression of p53-dependent osteosarcoma.
• YAP1 inactivation impacts key cellular processes and gene expression patterns in OS.
• This study provides molecular evidence supporting YAP1 as a potential therapeutic target in OS.