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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...

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Autores principales: Fang, Bangwei, Wei, Yu, Pan, Jian, Zhang, Tingwei, Ye, Dingwei, Zhu, Yao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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