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Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin

Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin
Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin
Normal sun-exposed skin contains numerous epidermal patches that stain positive for p53 protein (p53 immunopositive patches; PIPs), which are considered potential early precursors of skin cancer. Whilst the TP53 gene is mutated in many PIPs, it is unclear whether PIPs contain any other cancer-related mutations. Here we report that PIPs, predominantly <3,000 p53 immunopositive cells in size, within normal chronically exposed skin contain mutations in multiple genes which are mutated in cutaneous squamous cell cancers. These mutations in the PIPs were not detected within the non-PIP epidermis of corresponding normal chronically exposed skin. Although some of these genetic alterations are clonal in the PIPs, many of the mutations are subclonal within these lesions. Similar mutations are seen in later precancers (actinic keratoses and Bowen’s disease). Our results demonstrate that PIPs in chronically exposed skin contain multiple mutations in cancer-related genes. In addition, the results indicate that the clonal evolution of mutations which are seen within later precancerous lesions and in established malignancy can also occur in PIPs within normal human skin.
p53 immunopositive patches, p53 mutant patches, p53 mutant clones, actinic keratosis, Bowen's disease
0022-202X
Albibas, Amel, Abdulsalam M
0dccf7a0-80e6-4fd6-bad4-6d45131d6037
Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Lai, Chester
29ba48ea-2d38-497f-8cf9-400237f6a3a0
Pengelly, Reuben J
af97c0c1-b568-415c-9f59-1823b65be76d
Lockett, Gabrielle
836cb0d4-cd10-44fb-a1f6-71d24778d054
Theaker, Jeffery
97f1c7eb-24a8-48c3-8f69-ef23d51eb786
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Albibas, Amel, Abdulsalam M
0dccf7a0-80e6-4fd6-bad4-6d45131d6037
Rose-Zerilli, Matthew
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Lai, Chester
29ba48ea-2d38-497f-8cf9-400237f6a3a0
Pengelly, Reuben J
af97c0c1-b568-415c-9f59-1823b65be76d
Lockett, Gabrielle
836cb0d4-cd10-44fb-a1f6-71d24778d054
Theaker, Jeffery
97f1c7eb-24a8-48c3-8f69-ef23d51eb786
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd

Albibas, Amel, Abdulsalam M, Rose-Zerilli, Matthew, Lai, Chester, Pengelly, Reuben J, Lockett, Gabrielle, Theaker, Jeffery, Ennis, Sarah, Holloway, John and Healy, Eugene (2017) Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin Journal of Investigative Dermatology

Record type: Article

Abstract

Normal sun-exposed skin contains numerous epidermal patches that stain positive for p53 protein (p53 immunopositive patches; PIPs), which are considered potential early precursors of skin cancer. Whilst the TP53 gene is mutated in many PIPs, it is unclear whether PIPs contain any other cancer-related mutations. Here we report that PIPs, predominantly <3,000 p53 immunopositive cells in size, within normal chronically exposed skin contain mutations in multiple genes which are mutated in cutaneous squamous cell cancers. These mutations in the PIPs were not detected within the non-PIP epidermis of corresponding normal chronically exposed skin. Although some of these genetic alterations are clonal in the PIPs, many of the mutations are subclonal within these lesions. Similar mutations are seen in later precancers (actinic keratoses and Bowen’s disease). Our results demonstrate that PIPs in chronically exposed skin contain multiple mutations in cancer-related genes. In addition, the results indicate that the clonal evolution of mutations which are seen within later precancerous lesions and in established malignancy can also occur in PIPs within normal human skin.

Text Subclonal Evolution of Cancer-Related Gene Mutations in p53 Immunopositive Patches in Human Skin - Final accepted - Accepted Manuscript
Restricted to Repository staff only until 24 October 2018.

More information

Accepted/In Press date: 25 July 2017
Published date: 2017
Additional Information: Short title: Gene Mutations in p53 Immunopositive Patches
Keywords: p53 immunopositive patches, p53 mutant patches, p53 mutant clones, actinic keratosis, Bowen's disease

Identifiers

Local EPrints ID: 413007
URI: http://eprints.soton.ac.uk/id/eprint/413007
ISSN: 0022-202X
PURE UUID: 2900d0d4-59f5-4d1a-9ba2-2ef8c26eb888
ORCID for Reuben J Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 10 Aug 2017 16:31
Last modified: 23 Oct 2017 16:31

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