Moody Emily W, Vagher Jennie, Espinel Whitney, Goldgar David, Hagerty Kelsi J, Gammon Amanda
University of Utah, Salt Lake City, UT.
Huntsman Cancer Institute, Salt Lake City, UT.
JCO Precis Oncol. 2019 Dec;3:1-8. doi: 10.1200/PO.19.00144.
To compare the classification of genetic variants reported on tumor genomic profiling (TGP) reports with germline classifications on clinical test results and ClinVar. Results will help to inform germline testing discussions and decisions in patients with tumor variants in genes that are relevant to hereditary cancer risk.
This study compared somatic and germline classifications of small nucleotide variants in the following genes: , , , , , , , , and . Somatic classifications were taken from reports from a single commercial TGP laboratory of tests ordered by providers at Huntsman Cancer Institute between March 2014 and June 2018. Somatic variant interpretations were compared with classifications from germline test results as well as with ClinVar interpretations.
Of the 623 variants identified on TGP, 353 had a definitive classification in ClinVar, and 103 were assayed with a germline test, with 66 of the variants tested observed in germline. Analysis of somatic variants of uncertain significance listed on TGP reports determined that 22% had a different interpretation compared with ClinVar and that 32% differed from the interpretation on a germline test result. Pathogenic variants on TGP test results were found to differ 13% and 5% of the time compared with ClinVar interpretations and germline test results, respectively.
These results suggest that TGP variants are often classified differently in a germline context. Differences may be due to different processes in variant interpretation between somatic and germline laboratories. These results are important for health care providers to consider when making decisions about additional testing for hereditary cancer risks.
比较肿瘤基因组图谱（TGP）报告中所报道的基因变异分类与临床检测结果及临床变异数据库（ClinVar）中的种系分类。研究结果将有助于为遗传性癌症风险相关基因存在肿瘤变异的患者进行种系检测的讨论和决策提供参考。
本研究比较了以下基因中小核苷酸变异的体细胞和种系分类： 、 、 、 、 、 、 、 和 。体细胞分类取自2014年3月至2018年6月期间亨茨曼癌症研究所的医疗服务提供者订购的单一商业TGP实验室的检测报告。将体细胞变异解释与种系检测结果的分类以及ClinVar解释进行比较。
在TGP上鉴定出的623个变异中，353个在ClinVar中有明确分类，103个进行了种系检测，其中66个变异在种系中被检测到。对TGP报告中列出的意义未明的体细胞变异进行分析，结果显示，与ClinVar相比，22%的变异有不同解释，与种系检测结果的解释相比，32%的变异存在差异。发现TGP检测结果中的致病性变异与ClinVar解释和种系检测结果相比，分别有13%和5%的差异。
这些结果表明，TGP变异在种系背景下的分类通常不同。差异可能是由于体细胞和种系实验室在变异解释过程中的不同。这些结果对于医疗服务提供者在就遗传性癌症风险的额外检测做出决策时具有重要参考价值。
