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Genetics and Genomics

Is loss of p53 a driver of ductal carcinoma in situ progression?

British Journal of Cancer volume 127, pages 1744–1754 (2022)Cite this article

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Abstract

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15–30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS and highlight the need for functional studies of the role of TP53 in the development of DCIS and progression from DCIS to invasive disease.

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Fig. 1: Schematic of breast cancer progression from a normal duct to an invasive carcinoma.
Fig. 2: Morphological subtypes of DCIS (solid, cribriform, papillary, micropapillary and comedo).
Fig. 3: Lollipop chart displaying frequency and distribution of TP53 mutations in DCIS (top) and breast cancer (bottom).

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Funding

This work was supported by the NIH/NCI under award number F31CA246917, the Cancer Prevention Research Institute of Texas under award number RP180313 and Cancer Research UK and KWF Kankerbestrijding (ref. C38317/A24043).

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Authors and Affiliations

  1. Genetics and Epigenetics Program at The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA

    Rhiannon L. Morrissey & Guillermina Lozano

  2. Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rhiannon L. Morrissey & Guillermina Lozano

  3. Division of Surgical Oncology, Department of Surgery, Baylor College of Medicine, Houston, TX, USA

    Alastair M. Thompson

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  1. Rhiannon L. Morrissey
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RLM, AMT and GL wrote and revised the manuscript.

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Correspondence to Guillermina Lozano.

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Morrissey, R.L., Thompson, A.M. & Lozano, G. Is loss of p53 a driver of ductal carcinoma in situ progression?. Br J Cancer 127, 1744–1754 (2022). https://doi.org/10.1038/s41416-022-01885-5

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  • DOI: https://doi.org/10.1038/s41416-022-01885-5

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