Somatic Testing and Germline Genetic Status: Implications for Cancer Treatment Decisions and Genetic Counseling

Swan, Kelli; Dougherty, Kali Chatham; Myers, Sara Wienke

doi:10.1007/s40142-020-00192-w

Cited by 1 publication

(2 citation statements)

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“…Germline testing for heritable variants is now recommended for all patients with epithelial ovarian cancers, and both management strategies and treatments have been developed based on testing results 4 . For nearly a decade, germline BRCA1/2 pathogenic variants have been established indicators of platinum sensitivity and PARP inhibitor eligibility for these patients 5 . Germline testing also presents opportunities for cascade testing and disease prevention within families.…”

Section: Introductionmentioning

confidence: 99%

“… 4 For nearly a decade, germline BRCA1/2 pathogenic variants have been established indicators of platinum sensitivity and PARP inhibitor eligibility for these patients. 5 Germline testing also presents opportunities for cascade testing and disease prevention within families. For example, National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of risk‐reducing surgery for patients with pathogenic BRCA1 , BRCA2 , BRIP1 , RAD51C , RAD51D , MLH1 , and MSH2 germline variants based on the associated high relative risks of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

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Landscape of potential germline pathogenic variants in select cancer susceptibility genes in patients with adult‐type ovarian granulosa cell tumors

Summey,

Gornstein,

Decker

et al. 2024

Cancer Medicine

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ObjectiveThe objective of this study was to assess the frequency of potential germline pathogenic variants that may contribute to risk of development of adult granulosa cell tumors (AGCT) given the paucity of germline testing guidelines for these patients.MethodsThis was a retrospective cross‐sectional study analyzing comprehensive genomic profiling (CGP) results of AGCT with the FOXL2 p.C134W mutation submitted to Foundation Medicine between 2012 and 2022. Cases with a potential germline pathogenic variant were identified by filtering single nucleotide variants and short indels by variant allele frequency (VAF) and presence in ClinVar for select cancer susceptibility genes. Odds ratios for AGCT risk were calculated compared to a healthy population.ResultsPrior to analysis, 595 patients were screened and 516 with a somatic FOXL2 p.C134W mutation were included. Potential germline pathogenic variants in a DNA repair‐related gene (ATM, BRCA1, BRCA2, CHEK2, PALB2, PMS2, RAD51C, or RAD51D) were found in 6.6% of FOXL2‐mutated AGCT. Potential germline pathogenic CHEK2 variants were found in 3.5% (18/516) of AGCT patients, a rate that was 2.8‐fold higher than Genome Aggregation Database non‐cancer subjects (95% CI 1.8–4.6, p < 0.001). The founder variants p.I157T (38.9%, 7/18) and p.T367fs*15 (c.1100delC; 27.8%, 5/18) were most commonly observed. CHEK2 VAF indicated frequent loss of the wildtype copy of the gene.ConclusionsThese results support ongoing utilization of genomic tumor profiling and confirmatory germline testing for potential germline pathogenic variants. Further prospective investigation into the biology of germline variants in this population is warranted.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%