Comparative analysis of TP53 gene in Tupaia belangeri subspecies ( Tupaia belangeri yaoshanensis vs. Tupaia belangeri chinensis ) and identification of mutations in spontaneous tumor cases
Comparative genomic analysis reveals high TP53 conservation and tumor variants in tree shrews, highlighting their potential as cancer models.
Key Points
To characterize the TP53 coding sequence across Tupaia belangeri subspecies and identify potential TP53 mutations in spontaneous tumors.
Sequenced the entire TP53 coding sequence across two tree shrew subspecies (T. b. yaoshanensis and T. b. chinensis).
Characterized two spontaneous sarcomas from T. b. yaoshanensis using histopathology, immunohistochemistry, structural modeling, and cDNA sequencing with clonal validation.
TP53 coding sequences showed 99.5% nucleotide identity between subspecies, strict conservation of human cancer hotspot residues, and structural alignment to human p53 (RMSD = 0.6 Å).
Identified spontaneous tumor variants including a Ser175Gly missense change in the DNA-binding domain of a liposarcoma and a Met344Thr change in the tetramerization domain of a myxofibrosarcoma (SIFT scores 0.61 and 0.77).