講演情報
[PE5-3]生殖細胞系列と体細胞の統合されたがん検査におけるリスクの特定と変異の起源を解決する機会の提供
○西口 礼子1, Kingshuk Das2, Amber Carter2, Brandie Heald2, Scott Michalski2, Sarah Nielsen2, Nhu Ngo2, Sara Elrefai3, Kelly Warsinske3, Stacy Lenarcic3, Heather Hampel4, Robert Nussbaum2, Edward Esplin2 (1.インヴィティ ジャパン株式会社 グローバルメディカルアフェアーズ部, 2.Invitae Inc., San Francisco, USA, 3.Atrium Health, Charlotte, USA, 4.The Ohio State University Medical Center, Columbus, USA)
Objective
Germline and somatic genetic testing are established for the management of cancer patients. Somatic testing is used to inform therapy and germline testing to diagnose hereditary cancer predisposition. While somatic testing can detect germline variants, the reporting is optimized for therapeutic efficacy. Germline variants may be missed or misinterpreted. We reviewed a series of patients who received both germline and somatic testing to examine the opportunities for concurrent testing to improve somatic reporting.
Method
We reviewed 43 patients with solid cancer who were tested with a 435 gene somatic genetic test and an 83 gene germline test. The most frequent cancers were pancreatic, ovarian, and prostate.
Results
16% harbored a pathogenic or likely pathogenic germline variant in a cancer susceptibility gene, including MLH1, MSH6, CHEK2, PALB2, CDKN2A, NBN, and MUTYH. 93% had at least one variant detected by somatic testing in the germline panel genes. These variants were within the reportable range of the germline assay, and the germline test resolved their germline vs somatic origins. The genes that most frequently had somatic variants were TP53, CDKN2A, SMAD4, and FLCN.
Conclusion
There is a high probability of detecting variants in hereditary cancer predisposition genes in common somatic gene panels. Since a high proportion of cancer patients harbor PGVs, which can inform treatment, surveillance, prevention and risk for family, it is crucial to resolve the somatic vs germline origin. Concurrent testing can be advantageous to glean this crucial information.
Germline and somatic genetic testing are established for the management of cancer patients. Somatic testing is used to inform therapy and germline testing to diagnose hereditary cancer predisposition. While somatic testing can detect germline variants, the reporting is optimized for therapeutic efficacy. Germline variants may be missed or misinterpreted. We reviewed a series of patients who received both germline and somatic testing to examine the opportunities for concurrent testing to improve somatic reporting.
Method
We reviewed 43 patients with solid cancer who were tested with a 435 gene somatic genetic test and an 83 gene germline test. The most frequent cancers were pancreatic, ovarian, and prostate.
Results
16% harbored a pathogenic or likely pathogenic germline variant in a cancer susceptibility gene, including MLH1, MSH6, CHEK2, PALB2, CDKN2A, NBN, and MUTYH. 93% had at least one variant detected by somatic testing in the germline panel genes. These variants were within the reportable range of the germline assay, and the germline test resolved their germline vs somatic origins. The genes that most frequently had somatic variants were TP53, CDKN2A, SMAD4, and FLCN.
Conclusion
There is a high probability of detecting variants in hereditary cancer predisposition genes in common somatic gene panels. Since a high proportion of cancer patients harbor PGVs, which can inform treatment, surveillance, prevention and risk for family, it is crucial to resolve the somatic vs germline origin. Concurrent testing can be advantageous to glean this crucial information.