Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers
Abstract The promising expectations about personalized medicine have opened the path to routine large-scale sequencing and increased the importance of genetic counseling for hereditary cancers, among which hereditary breast and ovary cancers (HBOC) have a major impact. High-throughput sequencing, or...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-020-01554-6 |
| _version_ | 1811327487689359360 |
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| author | Giulia Federici Silvia Soddu |
| author_facet | Giulia Federici Silvia Soddu |
| author_sort | Giulia Federici |
| collection | DOAJ |
| description | Abstract The promising expectations about personalized medicine have opened the path to routine large-scale sequencing and increased the importance of genetic counseling for hereditary cancers, among which hereditary breast and ovary cancers (HBOC) have a major impact. High-throughput sequencing, or Next-Generation Sequencing (NGS), has improved cancer patient management, ameliorating diagnosis and treatment decisions. In addition to its undeniable clinical utility, NGS is also unveiling a large number of variants that we are still not able to clearly define and classify, the variants of uncertain significance (VUS), which account for about 40% of total variants. At present, VUS use in the clinical context is challenging. Medical reports may omit this kind of data and, even when included, they limit the clinical utility of genetic information. This has prompted the scientific community to seek easily applicable tests to accurately classify VUS and increase the amount of usable information from NGS data. In this review, we will focus on NGS and classification systems for VUS investigation, with particular attention on HBOC-related genes and in vitro functional tests developed for ameliorating and accelerating variant classification in cancer. |
| first_indexed | 2024-04-13T15:07:39Z |
| format | Article |
| id | doaj.art-4f32f07d62474cd297ad1c92f8a847fe |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T15:07:39Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-4f32f07d62474cd297ad1c92f8a847fe2022-12-22T02:42:06ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662020-03-0139111210.1186/s13046-020-01554-6Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancersGiulia Federici0Silvia Soddu1Cellular Networks and Molecular Therapeutic Targets Unit, Department of Research and Advanced Technologies, IRCCS-Regina Elena National Cancer InstituteCellular Networks and Molecular Therapeutic Targets Unit, Department of Research and Advanced Technologies, IRCCS-Regina Elena National Cancer InstituteAbstract The promising expectations about personalized medicine have opened the path to routine large-scale sequencing and increased the importance of genetic counseling for hereditary cancers, among which hereditary breast and ovary cancers (HBOC) have a major impact. High-throughput sequencing, or Next-Generation Sequencing (NGS), has improved cancer patient management, ameliorating diagnosis and treatment decisions. In addition to its undeniable clinical utility, NGS is also unveiling a large number of variants that we are still not able to clearly define and classify, the variants of uncertain significance (VUS), which account for about 40% of total variants. At present, VUS use in the clinical context is challenging. Medical reports may omit this kind of data and, even when included, they limit the clinical utility of genetic information. This has prompted the scientific community to seek easily applicable tests to accurately classify VUS and increase the amount of usable information from NGS data. In this review, we will focus on NGS and classification systems for VUS investigation, with particular attention on HBOC-related genes and in vitro functional tests developed for ameliorating and accelerating variant classification in cancer.http://link.springer.com/article/10.1186/s13046-020-01554-6Next-generation sequencingGermline and somatic mutationsVariant classificationVariants of uncertain significanceFunctional testsATM gene |
| spellingShingle | Giulia Federici Silvia Soddu Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers Journal of Experimental & Clinical Cancer Research Next-generation sequencing Germline and somatic mutations Variant classification Variants of uncertain significance Functional tests ATM gene |
| title | Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers |
| title_full | Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers |
| title_fullStr | Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers |
| title_full_unstemmed | Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers |
| title_short | Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers |
| title_sort | variants of uncertain significance in the era of high throughput genome sequencing a lesson from breast and ovary cancers |
| topic | Next-generation sequencing Germline and somatic mutations Variant classification Variants of uncertain significance Functional tests ATM gene |
| url | http://link.springer.com/article/10.1186/s13046-020-01554-6 |
| work_keys_str_mv | AT giuliafederici variantsofuncertainsignificanceintheeraofhighthroughputgenomesequencingalessonfrombreastandovarycancers AT silviasoddu variantsofuncertainsignificanceintheeraofhighthroughputgenomesequencingalessonfrombreastandovarycancers |