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The tumour suppressor p53 is activated following genotoxic stress and regulates the expression of target genes involved in the DNA damage response (DDR). The discovery that p53 isoforms alter the transcription of p53 target genes or p53 protein interactions unveiled an alternative DDR. This review will focus on the role p53 isoforms play in response to DNA damage. The expression of the C-terminally truncated p53 isoforms may be modulated via DNA damage-induced alternative splicing, whereas alternative translation plays an important role in modulating the expression of N-terminally truncated isoforms. The DDR induced by p53 isoforms may enhance the canonical p53 DDR or block cell death mechanisms in a DNA damage- and cell-specific manner, which could contribute to chemoresistance in a cancer context. Thus, a better understanding of the involvement of p53 isoforms in the cell fate decisions could uncover potential therapeutic targets in cancer and other diseases., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node., (Copyright © 2021. Published by Elsevier Inc.)