CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant

CCNB2 和 AURKA 过度表达可能导致日本皮质醇分泌肾上腺皮质癌中出现 TP53 体细胞变异的非典型有丝分裂

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作者:Akira Ikeya, Mitsuko Nakashima, Miho Yamashita, Keisuke Kakizawa, Yuta Okawa, Hirotomo Saitsu, Shigekazu Sasaki, Hironobu Sasano, Takafumi Suda, Yutaka Oki

Background

Many genomic analyses of cortisol-producing adrenocortical carcinoma (ACC) have been reported, but very few have come from East Asia. The first

Conclusion

We believe this is the first report that discusses the relationship between atypical mitotic figures and TP53 somatic variant in ACC. We presumed that overexpression of CCNB2 and AURKA mRNA may cause atypical mitosis in TP53 somatic mutated cases. Because AURKA is highly expressed in atypical mitotic cases, it may be an appropriate indicator for AURKA inhibitors.

Results

Six possible pathogenic and one uncertain significance somatic variants including a novel PRKAR1A (NM_002734.4):c.545C>A (p.T182K) variant were found in five of seven cases. By integrating these data with pathological findings, we hypothesized that cases with TP53 variants were more likely to show atypical mitotic figures. Using TCGA dataset, we found that atypical mitotic figures were associated with TP53 somatic variant, and mRNA expression of CCNB2 and AURKA was significantly high in TP53 mutated cases and atypical mitotic figure cases.

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