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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doaj-3ffa3c6653334cbc9755ec544c1a6c2f2020-11-24T22:27:54ZengKarger 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 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Steven Sorscher Shakti Ramkissoon |
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 |
author_facet |
Steven Sorscher Shakti Ramkissoon |
author_sort |
Steven Sorscher |
title |
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_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_sort |
next-generation sequencing in order to better characterize a brca variant of uncertain significance |
publisher |
Karger Publishers |
series |
Case Reports in Oncology |
issn |
1662-6575 |
publishDate |
2017-07-01 |
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. |
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 |
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