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Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach

BACKGROUND: Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between primary and metastatic CMM. In the present study, we performed next-generation sequ...

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Autores principales: Manca, Antonella, Paliogiannis, Panagiotis, Colombino, Maria, Casula, Milena, Lissia, Amelia, Botti, Gerardo, Caracò, Corrado, Ascierto, Paolo A., Sini, Maria Cristina, Palomba, Grazia, Pisano, Marina, Doneddu, Valentina, Cossu, Antonio, Palmieri, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712827/
https://www.ncbi.nlm.nih.gov/pubmed/31455347
http://dx.doi.org/10.1186/s12967-019-2039-4
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author Manca, Antonella
Paliogiannis, Panagiotis
Colombino, Maria
Casula, Milena
Lissia, Amelia
Botti, Gerardo
Caracò, Corrado
Ascierto, Paolo A.
Sini, Maria Cristina
Palomba, Grazia
Pisano, Marina
Doneddu, Valentina
Cossu, Antonio
Palmieri, Giuseppe
author_facet Manca, Antonella
Paliogiannis, Panagiotis
Colombino, Maria
Casula, Milena
Lissia, Amelia
Botti, Gerardo
Caracò, Corrado
Ascierto, Paolo A.
Sini, Maria Cristina
Palomba, Grazia
Pisano, Marina
Doneddu, Valentina
Cossu, Antonio
Palmieri, Giuseppe
author_sort Manca, Antonella
collection PubMed
description BACKGROUND: Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between primary and metastatic CMM. In the present study, we performed next-generation sequencing (NGS) analysis of the main genes participating in melanoma pathogenesis and progression, among paired primary and metastatic lesions of CMM patients, with the aim to evaluate levels of discrepancies in mutational patterns. METHODS: Paraffin-embedded tumor tissues of the paired lesions were retrieved from the archives of the institutions participating in the study. NGS was performed using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup (IMI) to explore the mutational status of selected regions (343 amplicons; amplicon range: 125–175 bp; coverage 100%) within the main 25 genes involved in CMM pathogenesis; sequencing was performed with the Ion Torrent PGM System. RESULTS: A discovery cohort encompassing 30 cases, and a validation cohort including eleven Sardinian patients with tissue availability from both the primary and metachronous metastatic lesions were identified; the global number of analyzed tissue specimens was 90. A total of 829 genetic non-synonymous variants were detected: 101 (12.2%) were pathogenic/likely pathogenic, 131 (15.8%) were benign/likely benign, and the remaining 597 (72%) were uncertain/unknown significance variants. Considering the global cohort, the consistency in pathogenic/pathogenic like mutations was 76%. Consistency for BRAF and NRAS mutations was 95.2% and 85.7% respectively, without statistically significant differences between the discovery and validation cohort. CONCLUSIONS: Our study showed a high level of concordance in mutational patterns between primary and metastatic CMM, especially when pathogenic mutations in driver genes were considered.
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spelling pubmed-67128272019-08-29 Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach Manca, Antonella Paliogiannis, Panagiotis Colombino, Maria Casula, Milena Lissia, Amelia Botti, Gerardo Caracò, Corrado Ascierto, Paolo A. Sini, Maria Cristina Palomba, Grazia Pisano, Marina Doneddu, Valentina Cossu, Antonio Palmieri, Giuseppe J Transl Med Research BACKGROUND: Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between primary and metastatic CMM. In the present study, we performed next-generation sequencing (NGS) analysis of the main genes participating in melanoma pathogenesis and progression, among paired primary and metastatic lesions of CMM patients, with the aim to evaluate levels of discrepancies in mutational patterns. METHODS: Paraffin-embedded tumor tissues of the paired lesions were retrieved from the archives of the institutions participating in the study. NGS was performed using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup (IMI) to explore the mutational status of selected regions (343 amplicons; amplicon range: 125–175 bp; coverage 100%) within the main 25 genes involved in CMM pathogenesis; sequencing was performed with the Ion Torrent PGM System. RESULTS: A discovery cohort encompassing 30 cases, and a validation cohort including eleven Sardinian patients with tissue availability from both the primary and metachronous metastatic lesions were identified; the global number of analyzed tissue specimens was 90. A total of 829 genetic non-synonymous variants were detected: 101 (12.2%) were pathogenic/likely pathogenic, 131 (15.8%) were benign/likely benign, and the remaining 597 (72%) were uncertain/unknown significance variants. Considering the global cohort, the consistency in pathogenic/pathogenic like mutations was 76%. Consistency for BRAF and NRAS mutations was 95.2% and 85.7% respectively, without statistically significant differences between the discovery and validation cohort. CONCLUSIONS: Our study showed a high level of concordance in mutational patterns between primary and metastatic CMM, especially when pathogenic mutations in driver genes were considered. BioMed Central 2019-08-28 /pmc/articles/PMC6712827/ /pubmed/31455347 http://dx.doi.org/10.1186/s12967-019-2039-4 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Manca, Antonella
Paliogiannis, Panagiotis
Colombino, Maria
Casula, Milena
Lissia, Amelia
Botti, Gerardo
Caracò, Corrado
Ascierto, Paolo A.
Sini, Maria Cristina
Palomba, Grazia
Pisano, Marina
Doneddu, Valentina
Cossu, Antonio
Palmieri, Giuseppe
Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
title Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
title_full Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
title_fullStr Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
title_full_unstemmed Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
title_short Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
title_sort mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712827/
https://www.ncbi.nlm.nih.gov/pubmed/31455347
http://dx.doi.org/10.1186/s12967-019-2039-4
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