Abstract 4649: Proposal of the concept of “<i>p53</i> mutational spectrum”: Its clinical implication in oral squamous cell carcinoma
Authors: Toshiki Hyodo, Nobuyuki Kuribayashi, Chonji Fukumoto, Yuske Komiyama, Tomonori Hasegawa, Koh-ichi Nakashiro, Daisuke Uchida, Hitoshi Kawamata
Journal: Cancer Research (2025)

Abstract The p53 gene is the most frequently mutated gene in malignant tumors. We found that p53 abnormalities were observed in most cases of oral squamous cell carcinoma (OSCC). Therefore, it is necessary to search for type of the functional abnormality (complete loss of function, partial loss of function, or gain of oncogenic function) of the p53 gene rather than the presence or absence of gene mutation. Here we would like to propose the concept “p53 mutational spectrum”. In this study we performed whole-exome sequencing of p53 using clinical specimens from OSCC and attempted to clarify the implication of “p53 mutational spectrum” with clinical manifestation. Sixty-seven patients with OSCC who visited the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University or Ehime University were subjected to the study. Genomic DNA was extracted from biopsy and surgical specimens, and a custom panel was created for OSCC. p53 and other driver gene mutations were analyzed by NGS. p53 mutation pattern was classified into 5 categories, wild type without p16 expression, wild type with p16 expression, missense mutations in the DNA binding domain, missense mutations out of the DNA binding domain and truncation mutations. Patients with several p53 mutational patterns were statistically analyzed in relation to biological and clinical grade, and overall survival (OS) and disease-free survival (DFS) were also analyzed. The patterns of p53 gene was wild type without p16 expression in 7 patients, wild type with p16 expression in 6 patients, missense mutations in the DNA binding domain in 31 patients, missense mutations out of the DNA binding domain in 2 patients and truncation mutations in 7 patients. Thus, the p53 gene was mutated in 54 patients, 33 with missense mutations and 24 with truncation mutations. p53 mutation distribution was concentrated in the DNA binding domain and missense mutations were common, while truncation mutations were common in other domains such as the transcriptional activation domain. In univariate analysis, p53 truncation mutations were identified as a risk factor for DFS and were associated with poorer prognosis compared with other mutation groups. p53 mutational spectrum was not significantly associated with other driver gene mutations. p53 missense mutation group. The p53 missense mutationp group was also analyzed in the same way, but the results were not statistically significant. The p53 truncation mutation (complete loss of function) was associated with poorer prognosis than other gene status, wild type with/without p16 and missense mutation. The p53 missense mutation may contain functional diversity (complete loss of function, partial loss of function, almost wild, or gain of oncogenic function). We are currently constructing a platform for p53 mutational spectrum database. Citation Format: Toshiki Hyodo, Nobuyuki Kuribayashi, Chonji Fukumoto, Yuske Komiyama, Tomonori Hasegawa, Koh-ichi Nakashiro, Daisuke Uchida, Hitoshi Kawamata. Proposal of the concept of “p53 mutational spectrum”: Its clinical implication in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4649.