Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata.

Autor:	Kipnis LM; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts., Breen KM; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts., Koeller DR; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts., Levine AS; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts., Yang Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Jun H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Tayob N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts., Stokes SM; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Hayes CP; Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts., Ghazani AA; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts., Hill SJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts., Rana HQ; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2024 May 02; Vol. 17 (5), pp. 201-208.
DOI:	10.1158/1940-6207.CAPR-23-0535
Abstrakt:	Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata. Prevention Relevance: Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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