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Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions

BAP-1 (BRCA1-associated protein 1) inactivated melanocytic lesions are a group of familial or sporadic lesions with unique histology and molecular features. They are of great clinical interest, at least in part due to the potential for malignant transformation and association with a familial cancer...

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Autores principales: Zhou, Yan, Nelson, Andrew C., He, Yuyu, Munro, Sarah A., Song, Kyu Young, Domingo-Musibay, Evidio, Giubellino, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774463/
https://www.ncbi.nlm.nih.gov/pubmed/35052351
http://dx.doi.org/10.3390/genes13010010
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author Zhou, Yan
Nelson, Andrew C.
He, Yuyu
Munro, Sarah A.
Song, Kyu Young
Domingo-Musibay, Evidio
Giubellino, Alessio
author_facet Zhou, Yan
Nelson, Andrew C.
He, Yuyu
Munro, Sarah A.
Song, Kyu Young
Domingo-Musibay, Evidio
Giubellino, Alessio
author_sort Zhou, Yan
collection PubMed
description BAP-1 (BRCA1-associated protein 1) inactivated melanocytic lesions are a group of familial or sporadic lesions with unique histology and molecular features. They are of great clinical interest, at least in part due to the potential for malignant transformation and association with a familial cancer predisposition syndrome. Here, we describe a patient with multiple spatially and temporally distinct melanocytic lesions with loss of BAP1 expression by immunohistochemistry. RNA sequencing was performed on three independent lesions spanning the morphologic spectrum: a benign nevus, an atypical tumor, and a melanoma arising from a pre-existing BAP1-inactivated nevus. The three lesions demonstrated largely distinct gene expression and mutational profiles. Gene expression analysis revealed that genes involved in receptor protein kinase pathways were progressively upregulated from nevus to melanoma. Moreover, a clear enrichment of genes regulated in response to UV radiation was found in the melanoma from this patient, as well as upregulation of MAPK pathway-related genes and several transcription factors related to melanomagenesis.
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spelling pubmed-87744632022-01-21 Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions Zhou, Yan Nelson, Andrew C. He, Yuyu Munro, Sarah A. Song, Kyu Young Domingo-Musibay, Evidio Giubellino, Alessio Genes (Basel) Article BAP-1 (BRCA1-associated protein 1) inactivated melanocytic lesions are a group of familial or sporadic lesions with unique histology and molecular features. They are of great clinical interest, at least in part due to the potential for malignant transformation and association with a familial cancer predisposition syndrome. Here, we describe a patient with multiple spatially and temporally distinct melanocytic lesions with loss of BAP1 expression by immunohistochemistry. RNA sequencing was performed on three independent lesions spanning the morphologic spectrum: a benign nevus, an atypical tumor, and a melanoma arising from a pre-existing BAP1-inactivated nevus. The three lesions demonstrated largely distinct gene expression and mutational profiles. Gene expression analysis revealed that genes involved in receptor protein kinase pathways were progressively upregulated from nevus to melanoma. Moreover, a clear enrichment of genes regulated in response to UV radiation was found in the melanoma from this patient, as well as upregulation of MAPK pathway-related genes and several transcription factors related to melanomagenesis. MDPI 2021-12-22 /pmc/articles/PMC8774463/ /pubmed/35052351 http://dx.doi.org/10.3390/genes13010010 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Yan
Nelson, Andrew C.
He, Yuyu
Munro, Sarah A.
Song, Kyu Young
Domingo-Musibay, Evidio
Giubellino, Alessio
Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions
title Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions
title_full Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions
title_fullStr Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions
title_full_unstemmed Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions
title_short Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions
title_sort gene expression and mutational profile in bap-1 inactivated melanocytic lesions of progressive malignancy from a patient with multiple lesions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774463/
https://www.ncbi.nlm.nih.gov/pubmed/35052351
http://dx.doi.org/10.3390/genes13010010
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