PT  - JOURNAL ARTICLE
AU  - MIN HAN
AU  - SHIGEO YAMAGUCHI
AU  - MAI ONISHI
AU  - TOMOAKI FUJII
AU  - MASAKI HOSOYA
AU  - XUAN WEN
AU  - HIDENORI KIDO
AU  - SHUNSUKE KATO
TI  - 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
AID  - 10.21873/anticanres.15707
DP  - 2022 May 01
TA  - Anticancer Research
PG  - 2277--2288
VI  - 42
IP  - 5
4099  - http://ar.iiarjournals.org/content/42/5/2277.short
4100  - http://ar.iiarjournals.org/content/42/5/2277.full
SO  - Anticancer Res2022 May 01; 42
AB  - 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.