التفاصيل البيبلوغرافية
| العنوان: |
Unexpected actionable genetic variants revealed by multigene panel testing of patients with uterine cancer. |
| المؤلفون: |
Heald, Brandie1 (AUTHOR), Mokhtary, Sara1 (AUTHOR), Nielsen, Sarah M.1 (AUTHOR), Rojahn, Susan1 (AUTHOR), Yang, Shan1 (AUTHOR), Michalski, Scott T.1 (AUTHOR), Esplin, Edward D.1 (AUTHOR) ed.esplin@invitae.com |
| المصدر: |
Gynecologic Oncology. Aug2022, Vol. 166 Issue 2, p344-350. 7p. |
| مصطلحات موضوعية: |
*HEREDITARY nonpolyposis colorectal cancer, *UTERINE cancer, *GENETIC variation, *CANCER patients, *CANCER genes, *GENETIC testing |
| مستخلص: |
Hereditary uterine cancer (UC) is traditionally associated with pathogenic/likely pathogenic germline variants (PGVs) in Lynch syndrome genes or PTEN ; however, growing evidence supports a role for other genes that may reveal new clinical management options. In this study we assessed the prevalence and potential clinical impact of PGVs identified in UC patients referred for comprehensive germline genetic testing that combined testing for Lynch syndrome, PTEN , and other cancer predisposition genes. Prevalence of PGVs in patients referred to a single clinical lab for germline genetic testing with an indication of uterine or endometrial cancer were retrospectively assessed and compared by syndrome type, patient age at testing, and self-reported ancestry. Potential clinical actionability of PGVs was based on established guidelines for clinical management, targeted therapies, and clinical trial eligibility. PGVs were detected in 13.6% of the cohort (880/6490). PGVs were most frequently observed in Lynch syndrome genes (60.4%) and PTEN (1.5%), with 38.1% in another cancer predisposition gene (i.e., CHEK2, BRCA1/BRCA2). PGV prevalence was similar for patients <50 years and those ≥50 years (15.1% vs 13.2%). Nearly all PGVs (97.2%) were associated with guideline-recommended management, including cascade testing; 60.5% were associated with FDA-approved therapies; and 35.2% were associated with clinical trials. Focusing germline testing on Lynch syndrome genes and PTEN and limiting testing to patients <50 years of age at diagnosis may overlook a substantial proportion of UC patients who harbor actionable PGVs. Universal comprehensive genetic testing of UC patients could benefit many patients and at-risk family members. • Pathogenic or likely pathogenic germline variants (PGVs) were found in 13.6% of uterine cancer patients tested. • Nearly 40% of PGVs were found outside of Lynch syndrome genes and PTEN. • The prevalences of PGVs in patients <50 years and ≥ 50 years at the time of testing were similar (15.1% vs 13.2%). • Sixty percent of PGVs were associated with FDA-approved therapies and 35% with precision therapy clinical trials. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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