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Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus
Primary malignant melanoma of the esophagus (PMME) is a rare gastrointestinal melanoma with a high rate of recurrence and metastasis. The standard of care for PMME has not been established yet due to a lack of understanding of its clinical and molecular pathogenesis. Thus, we performed genomic profi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166384/ https://www.ncbi.nlm.nih.gov/pubmed/35661532 http://dx.doi.org/10.1016/j.neo.2022.100811 |
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author | Li, Jingjing Guan, Wenyan Ren, Wei Liu, Ziyao Wu, Hongyan Chen, Yiqiang Liu, Siyuan Quan, Xiangming Yang, Zuoquan Jiang, Chong He, Jian Xiao, Xiao Ye, Qing |
author_facet | Li, Jingjing Guan, Wenyan Ren, Wei Liu, Ziyao Wu, Hongyan Chen, Yiqiang Liu, Siyuan Quan, Xiangming Yang, Zuoquan Jiang, Chong He, Jian Xiao, Xiao Ye, Qing |
author_sort | Li, Jingjing |
collection | PubMed |
description | Primary malignant melanoma of the esophagus (PMME) is a rare gastrointestinal melanoma with a high rate of recurrence and metastasis. The standard of care for PMME has not been established yet due to a lack of understanding of its clinical and molecular pathogenesis. Thus, we performed genomic profiling on a recurrent PMME case to seek novel opportunities for the management of this rare disease. Between 2013 and 2016, 6 tissue samples including 3 from the primary tumors, 2 from the relapsed tumors, and 1 from a normal control were collected from a patient diagnosed with PMME and were subjected to whole-exome sequencing to track the dynamic genetic changes. Additionally, we also analyzed a cohort of 398 samples obtained from the TCGA skin cutanesous melanoma (TCGA-SKCM) dataset to assess the frequency and determine the clinical implications of genomic events found in the presented study. ARHGAP35 (p.L1022M) was the only mutation shared across temporal PMME lesions. The PMME samples showed higher levels of genetic instability and intra-tumor heterogeneity. They also shared several concordant copy number variations (CNV). All lesions were concordant with the evolution trajectory, and shrinkage of the founding clone caused the subclonal population to become dominant in PT1c, which was likely the reason behind metastatic seeding. ARHGAP35 mutations were found in 6% of the TCGA-SKCM cohort samples. The presence of the mutations was associated with poor progression-free survival (PFS) by both univariate and multivariate Cox regression analyses. Our study showed that the primary tumor clone disseminates earlier in PMME. This highlights the need to understand the mechanism involved in the early PMME recurrence to optimize treatment. |
format | Online Article Text |
id | pubmed-9166384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91663842022-06-13 Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus Li, Jingjing Guan, Wenyan Ren, Wei Liu, Ziyao Wu, Hongyan Chen, Yiqiang Liu, Siyuan Quan, Xiangming Yang, Zuoquan Jiang, Chong He, Jian Xiao, Xiao Ye, Qing Neoplasia Original article Primary malignant melanoma of the esophagus (PMME) is a rare gastrointestinal melanoma with a high rate of recurrence and metastasis. The standard of care for PMME has not been established yet due to a lack of understanding of its clinical and molecular pathogenesis. Thus, we performed genomic profiling on a recurrent PMME case to seek novel opportunities for the management of this rare disease. Between 2013 and 2016, 6 tissue samples including 3 from the primary tumors, 2 from the relapsed tumors, and 1 from a normal control were collected from a patient diagnosed with PMME and were subjected to whole-exome sequencing to track the dynamic genetic changes. Additionally, we also analyzed a cohort of 398 samples obtained from the TCGA skin cutanesous melanoma (TCGA-SKCM) dataset to assess the frequency and determine the clinical implications of genomic events found in the presented study. ARHGAP35 (p.L1022M) was the only mutation shared across temporal PMME lesions. The PMME samples showed higher levels of genetic instability and intra-tumor heterogeneity. They also shared several concordant copy number variations (CNV). All lesions were concordant with the evolution trajectory, and shrinkage of the founding clone caused the subclonal population to become dominant in PT1c, which was likely the reason behind metastatic seeding. ARHGAP35 mutations were found in 6% of the TCGA-SKCM cohort samples. The presence of the mutations was associated with poor progression-free survival (PFS) by both univariate and multivariate Cox regression analyses. Our study showed that the primary tumor clone disseminates earlier in PMME. This highlights the need to understand the mechanism involved in the early PMME recurrence to optimize treatment. Neoplasia Press 2022-06-01 /pmc/articles/PMC9166384/ /pubmed/35661532 http://dx.doi.org/10.1016/j.neo.2022.100811 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Li, Jingjing Guan, Wenyan Ren, Wei Liu, Ziyao Wu, Hongyan Chen, Yiqiang Liu, Siyuan Quan, Xiangming Yang, Zuoquan Jiang, Chong He, Jian Xiao, Xiao Ye, Qing Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
title | Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
title_full | Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
title_fullStr | Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
title_full_unstemmed | Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
title_short | Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
title_sort | longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166384/ https://www.ncbi.nlm.nih.gov/pubmed/35661532 http://dx.doi.org/10.1016/j.neo.2022.100811 |
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