Akademska digitalna zbirka SLovenije - logo
E-viri
Celotno besedilo
Recenzirano Odprti dostop
  • Identification and Manageme...
    Bychkovsky, Brittany L; Li, Tianyu; Sotelo, Jilliane; Tayob, Nabihah; Mercado, Joanna; Gomy, Israel; Chittenden, Anu; Kane, Sarah; Stokes, Samantha; Hughes, Melissa E; Kim, Ji Seok; Umeton, Renato; Awad, Mark M; Konstantinopoulos, Panagiotis A; Yurgelun, Matthew B; Wolpin, Brian M; Taplin, Mary-Ellen; Newmark, Randall E; Johnson, Bruce E; Lindeman, Neal I; MacConaill, Laura E; Garber, Judy E; Lin, Nancy U

    Clinical cancer research, 2022-Jun-01, 2022-06-01, 20220601, Letnik: 28, Številka: 11
    Journal Article

    Tumor-only genomic testing can uncover somatic and germline pathogenic variants pathogenic/likely pathogenic (P/LP) in cancer predisposition genes. We describe the prevalence of P/LPs in BRCA1/2 and PALB2 (B1B2P2) across malignancies and the frequency of clinical germline testing (CGT) in patients with P/LPs in B1B2P2 identified on tumor-only testing. Among 7,575 patients with cancer tested between 2016 and 2018 with the OncoPanel tumor-only sequencing assay, we characterized P/LP frequencies by tumor type, receipt of CGT prior to or within 12 months after OncoPanel, and factors associated with CGT. 272 (3.6%) patients had OncoPanel-detected P/LPs in B1B2P2: 37.5% of P/LPs were in BRCA-related cancers; the remainder were in non-BRCA tumors. P/LPs were detected in ≥5% of breast, pancreatic, prostate, ovarian, nonmelanoma skin, endometrial, small cell lung, and colorectal cancers. 37.9% of patients with P/LPs received CGT prior to OncoPanel; an additional 10.7% underwent CGT within 12 months of OncoPanel. Among 132 with CGT, 88.6% had ≥1 clinical factor for CGT compared with 47.1% who did not undergo CGT. Patients with BRCA tumors were more likely to have CGT compared with those without (81.4% vs. 29.0%, P < 0.0001). Among patients with CGT, 70.5% (93/132) of P/LPs were germline. Tumor-only genomic testing identified P/LPs in B1B2P2 in 3.6% of patients. 52.9% of patients with tumor-detected P/LPs and without CGT did not meet personal or family history criteria for CGT. In addition, some patients with tumor-detected P/LPs were not referred for CGT, especially those with non-BRCA tumors. Given implications for treatment selection and familial cancer risk, processes to reliably trigger CGT from tumor-genomic findings are needed.