Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer

Truong, Hong; Breen, Kelsey; Nandakumar, Subhiksha; Sjoberg, Daniel D.; Kemel, Yelena; Mehta, Nikita; Reisz, Peter; Carruthers, Jessica; Benfante, Nicole; Vijai, Joseph; Khurram, Aliya; Gopalan, Anuradha; Fine, Samson W.; Reuter, Victor E.; Birsoy, Ozge; Liu, Ying; Walsh, Michael F.; Latham, Alicia; Mandelker, Diana; Stadler, Zsofia K.; Pietzak, Eugene J.; Ehdaie, Behfar; Touijer, Karim; Laudone, Vincent P.; Slovin, Susan F.; Autio, Karen A.; Danila, Daniel C.; Rathkopf, Dana E.; Eastham, James A.; Chen, Yu; Morris, Michael J.; Offit, Kenneth; Solit, David B.; Scher, Howard I.; Abida, Wassim; Carlo, Maria I.

doi:10.1016/j.eururo.2022.08.028

Cited by 11 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further studies showed even higher frequencies of genomic alterations, identifying up to 17.2% of included patients ( BRCA2 , 4.7%; CHEK2 , 2.9%; MUTYH , 2.4%; and ATM , 2.0%) 24 . On the other hand, germline variants are most frequently found for PCa harboring genomic alterations in PALB2 , CHEK2 , BRCA1 , BRCA2 , and ATM 25 . For instance, a germline ATM alteration is related to a 4-fold increase in PCa risk 26 .…”

Section: Germline Dna Damage Repair Alterations In Prostate Cancermentioning

confidence: 97%

“…For instance, a germline ATM alteration is related to a 4-fold increase in PCa risk 26 . Moreover, higher variant allele frequencies in next-generation sequencing results increase the probability of an underlying germline alteration 25 . HOXB13 is another gene in which germline alterations lead to an increased risk of PCa and are related to familial PCa 27 .…”

Section: Germline Dna Damage Repair Alterations In Prostate Cancermentioning

confidence: 99%

“… 24 On the other hand, germline variants are most frequently found for PCa harboring genomic alterations in PALB2 , CHEK2 , BRCA1 , BRCA2 , and ATM . 25 For instance, a germline ATM alteration is related to a 4-fold increase in PCa risk. 26 Moreover, higher variant allele frequencies in next-generation sequencing results increase the probability of an underlying germline alteration.…”

Section: Germline Dna Damage Repair Alterations In Prostate Cancermentioning

confidence: 99%

See 2 more Smart Citations

DNA Damage Response and Mismatch Repair Gene Defects in Advanced and Metastatic Prostate Cancer

Akhoundova,

Francica,

Rottenberg

et al. 2023

Advances in Anatomic Pathology

View full text Add to dashboard Cite

Alterations in DNA damage response (DDR) and related genes are present in up to 25% of advanced prostate cancers (PCa). Most frequently altered genes are involved in the homologous recombination repair, the Fanconi anemia, and the mismatch repair pathways, and their deficiencies lead to a highly heterogeneous spectrum of DDR-deficient phenotypes. More than half of these alterations concern non-BRCADDR genes. From a therapeutic perspective, poly-ADP-ribose polymerase inhibitors have demonstrated robust clinical efficacy in tumors withBRCA2andBRCA1alterations. Mismatch repair–deficient PCa, and a subset of CDK12-deficient PCa, are vulnerable to immune checkpoint inhibitors. Emerging data point to the efficacy of ATR inhibitors in PCa with ATM deficiencies. Still, therapeutic implications are insufficiently clarified for most of the non-BRCADDR alterations, and no successful targeted treatment options have been established.

show abstract

Section: Germline Dna Damage Repair Alterations In Prostate Cancermentioning

confidence: 97%

Section: Germline Dna Damage Repair Alterations In Prostate Cancermentioning

confidence: 99%

Section: Germline Dna Damage Repair Alterations In Prostate Cancermentioning

confidence: 99%

See 1 more Smart Citation

DNA Damage Response and Mismatch Repair Gene Defects in Advanced and Metastatic Prostate Cancer

Akhoundova,

Francica,

Rottenberg

et al. 2023

Advances in Anatomic Pathology

View full text Add to dashboard Cite

show abstract

“…The proportion of somatic BRCA1 mutation carriers among patients with mCRPC was available from five articles, for a total of 1243 patients, and was equal to 1.10% (95% CI: 0.60-1.76), without significant heterogeneity (I 2 = 0.00%; p = 0.8425) (Figure 2f). (f) proportion of patients with mCRPC with the somatic BRCA1 mutation [12][13][14][15][16][18][19][20][22][23][24][25][26][27][28][29][30][31][32][33][34][37][38][39][40][41][42][44][45][46][47][48][49][50][51].…”

Section: Proportion Of Patients With Mcrpc With Brca1 Mutationmentioning

confidence: 99%

“…Proportion of patients with prostate cancer harboring the BRCA2 mutation. (a) Proportion of patients with any stage PC with the germline BRCA2 mutation; (b) proportion of patients with any stage PC with the somatic BRCA2 mutation; (c) proportion of patients with metastatic PC with the germline BRCA2 mutation; (d) proportion of patients with metastatic PC with the somatic BRCA2 mutation; (e) proportion of patients with mCRPC with the germline BRCA2 mutation; and(f) proportion of patients with mCRPC with the somatic BRCA2 mutation[12,13,[15][16][17][18][19][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51].…”

mentioning

confidence: 99%

Frequency of Germline and Somatic BRCA1 and BRCA2 Mutations in Prostate Cancer: An Updated Systematic Review and Meta-Analysis

Valsecchi

Dionisio

Panepinto

et al. 2023

Cancers

View full text Add to dashboard Cite

In prostate cancer (PC), the presence of BRCA somatic and/or germline mutation provides prognostic and predictive information. Meta-analysis aims to estimate the frequency of BRCA mutations in patients with PC (PCp). In November 2022, we reviewed literature searching for all articles testing the proportion of BRCA mutations in PCp, without explicit enrichment for familiar risk. The frequency of germline and somatic BRCA1 and/or BRCA2 mutations was described in three stage disease populations (any/metastatic/metastatic castration-resistant PC, mCRPC). Out of 2253 identified articles, 40 were eligible. Here, 0.73% and 1.20% of any stage PCp, 0.94% and 1.10% of metastatic PCp, and 1.21% and 1.10% of mCRPC patients carried germline and somatic BRCA1 mutation, respectively; 3.25% and 6.29% of any stage PCp, 4.51% and 10.26% of metastatic PCp, and 3.90% and 10.52% of mCRPC patients carried germline and somatic BRCA2 mutation, respectively; and 4.47% and 7.18% of any stage PCp, 5.84% and 10.94% of metastatic PCp, and 5.26% and 11.26% of mCRPC patients carried germline and somatic BRCA1/2 mutation, respectively. Somatic mutations are more common than germline and BRCA2 are more common than BRCA1 mutations; the frequency of mutations is higher in the metastatic setting. Despite that BRCA testing in PC is now standard in clinical practice, several open questions remain.

show abstract

Prostate Cancer Genomic Testing: When Sequencing Is Not Sufficient and Germline Testing Is Necessary

Jacobs

Greenberg

2023

European Urology

View full text Add to dashboard Cite

Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer

Cited by 11 publications

References 31 publications

DNA Damage Response and Mismatch Repair Gene Defects in Advanced and Metastatic Prostate Cancer

DNA Damage Response and Mismatch Repair Gene Defects in Advanced and Metastatic Prostate Cancer

Frequency of Germline and Somatic BRCA1 and BRCA2 Mutations in Prostate Cancer: An Updated Systematic Review and Meta-Analysis

Prostate Cancer Genomic Testing: When Sequencing Is Not Sufficient and Germline Testing Is Necessary

Contact Info

Product

Resources

About