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Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart

Penoscrotum extramammary Paget disease (pEMPD) is a rare cutaneous carcinoma with an unknown cell origin. pEMPD always presents as a tumor in situ with an indolent process, whereas some progress into invasive forms with more aggressive behavior. The in situ and invasive cases display different morph...

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Autores principales: Rao, Yamin, Zhu, Jinchao, Zheng, Haiyan, Ren, Yong, Ji, Tianhai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451029/
https://www.ncbi.nlm.nih.gov/pubmed/36091120
http://dx.doi.org/10.3389/fonc.2022.972047
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author Rao, Yamin
Zhu, Jinchao
Zheng, Haiyan
Ren, Yong
Ji, Tianhai
author_facet Rao, Yamin
Zhu, Jinchao
Zheng, Haiyan
Ren, Yong
Ji, Tianhai
author_sort Rao, Yamin
collection PubMed
description Penoscrotum extramammary Paget disease (pEMPD) is a rare cutaneous carcinoma with an unknown cell origin. pEMPD always presents as a tumor in situ with an indolent process, whereas some progress into invasive forms with more aggressive behavior. The in situ and invasive cases display different morphologies and biological behavior, and thus far, a relationship between these two components has not been demonstrated. Immunohistochemistry was used to disclose the immunotype of pEMPD, and the results revealed that invasive/in situ pEMPD possessed with some identical immunophenotypes such as CK7, P63, and CK10, which inferred the clonal relatedness. The variable expressions of GCDFP-15 and carcino embryonic antigen hinted that tumor cell origin might be an epidermal sweat gland in epiderma. In our cohort, invasive pEMPD presented increased expression of androgen receptor and decreased MUC5CA expression, and these two changes might bring to the shift of invasive phenotype. To better understanding the relationship between these distinct tumor forms, we performed whole exome sequencing testing to evaluate overlapping genomic alterations of six paired invasive/in situ pEMPDs. The results showed that missense mutation was the predominant mutation type, and C>T transition accounted for 65.1% in all SNP mutation. Among the top 20 differential genes obtained from the six paired invasive/in situ pEMPD analysis, MUC4 (one missense, one in frame del, and one multi-hit), AHNAK2 (two missense and one multi-hit), DOT1L (two missense and one multi-hit), and FRG1 (two missense and one-multi hit) mutations were most enriched in invasive pEMPDs, which postulated that these genes may play roles in the disease progression.
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spelling pubmed-94510292022-09-08 Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart Rao, Yamin Zhu, Jinchao Zheng, Haiyan Ren, Yong Ji, Tianhai Front Oncol Oncology Penoscrotum extramammary Paget disease (pEMPD) is a rare cutaneous carcinoma with an unknown cell origin. pEMPD always presents as a tumor in situ with an indolent process, whereas some progress into invasive forms with more aggressive behavior. The in situ and invasive cases display different morphologies and biological behavior, and thus far, a relationship between these two components has not been demonstrated. Immunohistochemistry was used to disclose the immunotype of pEMPD, and the results revealed that invasive/in situ pEMPD possessed with some identical immunophenotypes such as CK7, P63, and CK10, which inferred the clonal relatedness. The variable expressions of GCDFP-15 and carcino embryonic antigen hinted that tumor cell origin might be an epidermal sweat gland in epiderma. In our cohort, invasive pEMPD presented increased expression of androgen receptor and decreased MUC5CA expression, and these two changes might bring to the shift of invasive phenotype. To better understanding the relationship between these distinct tumor forms, we performed whole exome sequencing testing to evaluate overlapping genomic alterations of six paired invasive/in situ pEMPDs. The results showed that missense mutation was the predominant mutation type, and C>T transition accounted for 65.1% in all SNP mutation. Among the top 20 differential genes obtained from the six paired invasive/in situ pEMPD analysis, MUC4 (one missense, one in frame del, and one multi-hit), AHNAK2 (two missense and one multi-hit), DOT1L (two missense and one multi-hit), and FRG1 (two missense and one-multi hit) mutations were most enriched in invasive pEMPDs, which postulated that these genes may play roles in the disease progression. Frontiers Media S.A. 2022-08-24 /pmc/articles/PMC9451029/ /pubmed/36091120 http://dx.doi.org/10.3389/fonc.2022.972047 Text en Copyright © 2022 Rao, Zhu, Zheng, Ren and Ji https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Rao, Yamin
Zhu, Jinchao
Zheng, Haiyan
Ren, Yong
Ji, Tianhai
Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart
title Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart
title_full Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart
title_fullStr Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart
title_full_unstemmed Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart
title_short Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart
title_sort cell origin and genome profile difference of penoscrotum invasive extramammary paget disease compared with its in situ counterpart
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451029/
https://www.ncbi.nlm.nih.gov/pubmed/36091120
http://dx.doi.org/10.3389/fonc.2022.972047
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