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The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer
Prostate cancers with mismatch repair deficiency (MMR-d) have aggressive clinical and histological features, and they are potentially responsive to immunotherapy. However, its rarity prevents the analysis of the underlying biology. Here, we collected the genomic data of 2664 primary prostate tumors...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864094/ https://www.ncbi.nlm.nih.gov/pubmed/36675550 http://dx.doi.org/10.3390/jcm12020623 |
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author | Fang, Bangwei Wei, Yu Pan, Jian Zhang, Tingwei Ye, Dingwei Zhu, Yao |
author_facet | Fang, Bangwei Wei, Yu Pan, Jian Zhang, Tingwei Ye, Dingwei Zhu, Yao |
author_sort | Fang, Bangwei |
collection | PubMed |
description | Prostate cancers with mismatch repair deficiency (MMR-d) have aggressive clinical and histological features, and they are potentially responsive to immunotherapy. However, its rarity prevents the analysis of the underlying biology. Here, we collected the genomic data of 2664 primary prostate tumors and 1409 metastatic prostate tumors from the GENIE and TCGA databases. A total of 69 (2.59%) primary and 60 (4.26%) metastatic MMR-d tumors were identified among these tumors. Single nucleotide variant (SNV) frequencies of 34 candidate genes (including KMT2D (46.4%), ZFHX3 (33.3%), JAK1 (31.9%), and RNF43 (27.5%)) and 16 candidate genes (including KMT2D (33.3%) and JAK1 (28.3%)) were higher in MMR-d primary tumors and MMR-d metastatic tumors, respectively. The tumor mutation burden (TMB) was higher in primary MMR-d tumors. Homozygous deletions of EPCAM and EPAS1 were enriched in MMR-d primary tumors, while EPCAM deletions were enriched in metastatic MMR-d tumors. For genomic rearrangement events, TMPRSS2-ETS fusions were less frequent in primary MMR-d tumors. Our study indicates MMR-d prostate cancers have unique genomic features. These may play an important role in providing therapeutic targets for the treatment of this subset of prostate cancer patients. |
format | Online Article Text |
id | pubmed-9864094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98640942023-01-22 The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer Fang, Bangwei Wei, Yu Pan, Jian Zhang, Tingwei Ye, Dingwei Zhu, Yao J Clin Med Article Prostate cancers with mismatch repair deficiency (MMR-d) have aggressive clinical and histological features, and they are potentially responsive to immunotherapy. However, its rarity prevents the analysis of the underlying biology. Here, we collected the genomic data of 2664 primary prostate tumors and 1409 metastatic prostate tumors from the GENIE and TCGA databases. A total of 69 (2.59%) primary and 60 (4.26%) metastatic MMR-d tumors were identified among these tumors. Single nucleotide variant (SNV) frequencies of 34 candidate genes (including KMT2D (46.4%), ZFHX3 (33.3%), JAK1 (31.9%), and RNF43 (27.5%)) and 16 candidate genes (including KMT2D (33.3%) and JAK1 (28.3%)) were higher in MMR-d primary tumors and MMR-d metastatic tumors, respectively. The tumor mutation burden (TMB) was higher in primary MMR-d tumors. Homozygous deletions of EPCAM and EPAS1 were enriched in MMR-d primary tumors, while EPCAM deletions were enriched in metastatic MMR-d tumors. For genomic rearrangement events, TMPRSS2-ETS fusions were less frequent in primary MMR-d tumors. Our study indicates MMR-d prostate cancers have unique genomic features. These may play an important role in providing therapeutic targets for the treatment of this subset of prostate cancer patients. MDPI 2023-01-12 /pmc/articles/PMC9864094/ /pubmed/36675550 http://dx.doi.org/10.3390/jcm12020623 Text en © 2023 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 Fang, Bangwei Wei, Yu Pan, Jian Zhang, Tingwei Ye, Dingwei Zhu, Yao The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer |
title | The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer |
title_full | The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer |
title_fullStr | The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer |
title_full_unstemmed | The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer |
title_short | The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer |
title_sort | somatic mutational landscape of mismatch repair deficient prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864094/ https://www.ncbi.nlm.nih.gov/pubmed/36675550 http://dx.doi.org/10.3390/jcm12020623 |
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