Germline Variants Identified in Patients with Early-onset Renal Cell Carcinoma Referred for Germline Genetic Testing.
Early-onset renal cell carcinoma
Genetic counseling
Germline sequencing
Hereditary renal cell carcinoma syndromes
Kidney cancer
Journal
European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
09
08
2021
revised:
08
09
2021
accepted:
20
09
2021
pubmed:
17
10
2021
medline:
3
2
2022
entrez:
16
10
2021
Statut:
ppublish
Résumé
Despite guidelines recommending genetic counseling for patients with early-onset renal cell carcinoma (RCC), studies interrogating the spectrum of germline mutations and clinical associations in patients with early-onset RCC are lacking. To define the germline genetic spectrum and clinical associations for patients with early-onset RCC diagnosed at age ≤46 yr who underwent genetic testing. We retrospectively identified patients with early-onset RCC who underwent germline testing at our institution from February 2003 to June 2020. The frequency and spectrum of pathogenic/likely pathogenic (P/LP) variants were determined. Clinical characteristics associated with mutation status were analyzed using two-sample comparison (Fisher's exact or χ Of 232 patients with early-onset RCC, 50% had non-clear-cell histology, including unclassified RCC (12.1%), chromophobe RCC (9.7%), FH-deficient RCC (7.0%), papillary RCC (6.6%), and translocation-associated RCC (4.3%). Overall, 43.5% had metastatic disease. Germline P/LP variants were identified in 41 patients (17.7%), of which 21 (9.1%) were in an RCC-associated gene and 20 (8.6%) in a non-RCC-associated gene, including 17 (7.3%) in DNA damage repair genes such as BRCA1/2, ATM, and CHEK2. Factors associated with RCC P/LP variants include bilateral/multifocal renal tumors, non-clear-cell histology, and additional extrarenal primary malignancies. In patients with only a solitary clear-cell RCC, the prevalence of P/LP variants in RCC-associated and non-RCC-associated genes was 0% and 9.9%, respectively. Patients with early-onset RCC had high frequencies of germline P/LP variants in genes associated with both hereditary RCC and other cancer predispositions. Germline RCC panel testing has the highest yield when patients have clinical phenotypes suggestive of underlying RCC gene mutations. Patients with early-onset RCC should undergo comprehensive assessment of personal and family history to guide appropriate genetic testing. In this study of 232 patients with early-onset kidney cancer who underwent genetic testing, we found a high prevalence of mutations in genes that increase the risk of cancer in both kidneys and other organs for patients and their at-risk family members. Our study suggests that patients with early-onset kidney cancer should undergo comprehensive genetic risk assessment.
Sections du résumé
BACKGROUND
Despite guidelines recommending genetic counseling for patients with early-onset renal cell carcinoma (RCC), studies interrogating the spectrum of germline mutations and clinical associations in patients with early-onset RCC are lacking.
OBJECTIVE
To define the germline genetic spectrum and clinical associations for patients with early-onset RCC diagnosed at age ≤46 yr who underwent genetic testing.
DESIGN, SETTING, AND PARTICIPANTS
We retrospectively identified patients with early-onset RCC who underwent germline testing at our institution from February 2003 to June 2020.
OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS
The frequency and spectrum of pathogenic/likely pathogenic (P/LP) variants were determined. Clinical characteristics associated with mutation status were analyzed using two-sample comparison (Fisher's exact or χ
RESULTS AND LIMITATIONS
Of 232 patients with early-onset RCC, 50% had non-clear-cell histology, including unclassified RCC (12.1%), chromophobe RCC (9.7%), FH-deficient RCC (7.0%), papillary RCC (6.6%), and translocation-associated RCC (4.3%). Overall, 43.5% had metastatic disease. Germline P/LP variants were identified in 41 patients (17.7%), of which 21 (9.1%) were in an RCC-associated gene and 20 (8.6%) in a non-RCC-associated gene, including 17 (7.3%) in DNA damage repair genes such as BRCA1/2, ATM, and CHEK2. Factors associated with RCC P/LP variants include bilateral/multifocal renal tumors, non-clear-cell histology, and additional extrarenal primary malignancies. In patients with only a solitary clear-cell RCC, the prevalence of P/LP variants in RCC-associated and non-RCC-associated genes was 0% and 9.9%, respectively.
CONCLUSIONS
Patients with early-onset RCC had high frequencies of germline P/LP variants in genes associated with both hereditary RCC and other cancer predispositions. Germline RCC panel testing has the highest yield when patients have clinical phenotypes suggestive of underlying RCC gene mutations. Patients with early-onset RCC should undergo comprehensive assessment of personal and family history to guide appropriate genetic testing.
PATIENT SUMMARY
In this study of 232 patients with early-onset kidney cancer who underwent genetic testing, we found a high prevalence of mutations in genes that increase the risk of cancer in both kidneys and other organs for patients and their at-risk family members. Our study suggests that patients with early-onset kidney cancer should undergo comprehensive genetic risk assessment.
Identifiants
pubmed: 34654685
pii: S2588-9311(21)00180-2
doi: 10.1016/j.euo.2021.09.005
pmc: PMC8688197
mid: NIHMS1747918
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
993-1000Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA082088
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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