TY - JOUR T1 - The <em>MDM2</em> and <em>CDKN2A</em> Copy-number-variation Influence the <em>TP53</em>-signature-score in Wild-type <em>TP53</em> Luminal Type Breast Cancer JF - Anticancer Research JO - Anticancer Res SP - 2277 LP - 2288 DO - 10.21873/anticanres.15707 VL - 42 IS - 5 AU - MIN HAN AU - SHIGEO YAMAGUCHI AU - MAI ONISHI AU - TOMOAKI FUJII AU - MASAKI HOSOYA AU - XUAN WEN AU - HIDENORI KIDO AU - SHUNSUKE KATO Y1 - 2022/05/01 UR - http://ar.iiarjournals.org/content/42/5/2277.abstract N2 - Background/Aim: The TP53-signature is a multi-gene signature that can predict TP53 structural mutations. It has presented remarkable ability to predict the prognosis of early-stage breast cancer. However, some samples presented discordance with the signature status and structure status. We aimed to investigate whether the mRNA expression levels or copy number variation (CNV) of MDM2 and CDKN2A influence the TP53-signature-score, subtype classification, and prognosis prediction in TP53 wild-type, luminal type early-stage breast cancer samples. Materials and Methods: We selected TP53 wild-type, luminal type early-stage breast cancer samples from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. Then, we analyzed the correlation between the TP53-signature-score and mRNA expression levels or CNV of MDM2 and CDKN2A. Results: The samples with MDM2 copy number (CN) amplification or those with CDKN2A CN deep deletion presented higher TP53-signature-score. Moreover, samples with MDM2 CN amplification or those with CDKN2A CN deep deletion had more characteristics of the luminal B type. In addition, they showed lower estrogen response early score, which correlated with response to endocrine therapy in breast cancer. However, MDM2 and CDKN2A mRNA expression did not present the same tendency. Furthermore, samples with MDM2 CN amplification or those with CDKN2A CN deep deletion had a worse prognosis in METABRIC cohort. Conclusion: The MDM2 or CDKN2A CNV may be useful for classifying subtypes and predicting prognosis more accurately in TP53 wild-type, luminal type early-stage breast cancer patients. ER -