Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance
BRCA germline mutations are the most common predisposing factor in familial breast-ovarian cancer syndrome families. However, many screened patients are identified as harboring BRCA variants of uncertain significance (VUS), rather than carrying deleterious germline mutations [Calo et al.: Cancers 20...
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| Format: | Article |
| Language: | English |
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Karger Publishers
2017-07-01
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| Series: | Case Reports in Oncology |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/478005 |
| _version_ | 1819084970517331968 |
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| author | Steven Sorscher Shakti Ramkissoon |
| author_facet | Steven Sorscher Shakti Ramkissoon |
| author_sort | Steven Sorscher |
| collection | DOAJ |
| description | BRCA germline mutations are the most common predisposing factor in familial breast-ovarian cancer syndrome families. However, many screened patients are identified as harboring BRCA variants of uncertain significance (VUS), rather than carrying deleterious germline mutations [Calo et al.: Cancers 2010; 2:1644–1660]. While such VUSs are typically reclassified as benign polymorphisms, this may occur years after the VUS is first identified [Murray et al.: Genet Med 2011; 13; 998–1005]. Loss of heterozygosity (LOH) of BRCA is nearly always the gatekeeper event in inherited BRCA-related breast cancer and LOH of BRCA is rare in sporadic cancers [Osorio et al.: Int J Cancer 2002; 99:305–309]. Here, we describe a patient identified as carrying a germline BRCA VUS. Tumor next-generation sequencing (NGS) demonstrated a very high mutation allelic frequency for that BRCA VUS, consistent with LOH. This case illustrates that since BRCA LOH is the typical mechanism of transformation in inherited BRCA-related breast cancers, NGS might be used to suggest that the BRCA VUS is actually cancer predisposing in a particular family. As a result, this may help patients make more informed decisions regarding screening and prophylactic therapy, long before official reclassification of the VUS occurs. |
| first_indexed | 2024-12-21T20:56:55Z |
| format | Article |
| id | doaj.art-3ffa3c6653334cbc9755ec544c1a6c2f |
| institution | Directory Open Access Journal |
| issn | 1662-6575 |
| language | English |
| last_indexed | 2024-12-21T20:56:55Z |
| publishDate | 2017-07-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Case Reports in Oncology |
| spelling | doaj.art-3ffa3c6653334cbc9755ec544c1a6c2f2022-12-21T18:50:32ZengKarger PublishersCase Reports in Oncology1662-65752017-07-0110263463710.1159/000478005478005Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain SignificanceSteven SorscherShakti RamkissoonBRCA germline mutations are the most common predisposing factor in familial breast-ovarian cancer syndrome families. However, many screened patients are identified as harboring BRCA variants of uncertain significance (VUS), rather than carrying deleterious germline mutations [Calo et al.: Cancers 2010; 2:1644–1660]. While such VUSs are typically reclassified as benign polymorphisms, this may occur years after the VUS is first identified [Murray et al.: Genet Med 2011; 13; 998–1005]. Loss of heterozygosity (LOH) of BRCA is nearly always the gatekeeper event in inherited BRCA-related breast cancer and LOH of BRCA is rare in sporadic cancers [Osorio et al.: Int J Cancer 2002; 99:305–309]. Here, we describe a patient identified as carrying a germline BRCA VUS. Tumor next-generation sequencing (NGS) demonstrated a very high mutation allelic frequency for that BRCA VUS, consistent with LOH. This case illustrates that since BRCA LOH is the typical mechanism of transformation in inherited BRCA-related breast cancers, NGS might be used to suggest that the BRCA VUS is actually cancer predisposing in a particular family. As a result, this may help patients make more informed decisions regarding screening and prophylactic therapy, long before official reclassification of the VUS occurs.http://www.karger.com/Article/FullText/478005BRCA variantVariant of uncertain significanceNext-generation sequencing |
| spellingShingle | Steven Sorscher Shakti Ramkissoon Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance Case Reports in Oncology BRCA variant Variant of uncertain significance Next-generation sequencing |
| title | Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance |
| title_full | Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance |
| title_fullStr | Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance |
| title_full_unstemmed | Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance |
| title_short | Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance |
| title_sort | next generation sequencing in order to better characterize a brca variant of uncertain significance |
| topic | BRCA variant Variant of uncertain significance Next-generation sequencing |
| url | http://www.karger.com/Article/FullText/478005 |
| work_keys_str_mv | AT stevensorscher nextgenerationsequencinginordertobettercharacterizeabrcavariantofuncertainsignificance AT shaktiramkissoon nextgenerationsequencinginordertobettercharacterizeabrcavariantofuncertainsignificance |