The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer
Abstract Carriers of germline BRCA2 pathogenic sequence variants have elevated aggressive prostate cancer risk and are candidates for precision oncology treatments. We examined whether BRCA2-deficient (BRCA2 d ) prostate tumors have distinct genomic alterations compared with BRCA2-intact (BRCA2 i )...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-06-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-022-00284-6 |
| _version_ | 1827608908682756096 |
|---|---|
| author | Kevin H. Kensler Shakuntala Baichoo Shailja Pathania Timothy R. Rebbeck |
| author_facet | Kevin H. Kensler Shakuntala Baichoo Shailja Pathania Timothy R. Rebbeck |
| author_sort | Kevin H. Kensler |
| collection | DOAJ |
| description | Abstract Carriers of germline BRCA2 pathogenic sequence variants have elevated aggressive prostate cancer risk and are candidates for precision oncology treatments. We examined whether BRCA2-deficient (BRCA2 d ) prostate tumors have distinct genomic alterations compared with BRCA2-intact (BRCA2 i ) tumors. Among 2536 primary and 899 metastatic prostate tumors from the ICGC, GENIE, and TCGA databases, we identified 138 primary and 85 metastatic BRCA2 d tumors. Total tumor mutation burden (TMB) was higher among primary BRCA2 d tumors, although pathogenic TMB did not differ by tumor BRCA2 status. Pathogenic and total single nucleotide variant (SNV) frequencies at KMT2D were higher in BRCA2 d primary tumors, as was the total SNV frequency at KMT2D in BRCA2 d metastatic tumors. Homozygous deletions at NEK3, RB1, and APC were enriched in BRCA2 d primary tumors, and RB1 deletions in metastatic BRCA2 d tumors as well. TMPRSS2-ETV1 fusions were more common in BRCA2 d tumors. These results identify somatic alterations that hallmark etiological and prognostic differences between BRCA2 d and BRCA2 i prostate tumors. |
| first_indexed | 2024-03-09T07:22:23Z |
| format | Article |
| id | doaj.art-e8bd40b686474509a6110e6ca54a55c3 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T07:22:23Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-e8bd40b686474509a6110e6ca54a55c32023-12-03T07:18:37ZengNature Portfolionpj Precision Oncology2397-768X2022-06-01611910.1038/s41698-022-00284-6The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancerKevin H. Kensler0Shakuntala Baichoo1Shailja Pathania2Timothy R. Rebbeck3Department of Population Health Sciences, Weill Cornell MedicineDepartment of Digital Technologies, FoICDT, University of MauritiusCenter for Personalized Cancer Therapy, University of MassachusettsDivision of Population Sciences, Dana-Farber Cancer InstituteAbstract Carriers of germline BRCA2 pathogenic sequence variants have elevated aggressive prostate cancer risk and are candidates for precision oncology treatments. We examined whether BRCA2-deficient (BRCA2 d ) prostate tumors have distinct genomic alterations compared with BRCA2-intact (BRCA2 i ) tumors. Among 2536 primary and 899 metastatic prostate tumors from the ICGC, GENIE, and TCGA databases, we identified 138 primary and 85 metastatic BRCA2 d tumors. Total tumor mutation burden (TMB) was higher among primary BRCA2 d tumors, although pathogenic TMB did not differ by tumor BRCA2 status. Pathogenic and total single nucleotide variant (SNV) frequencies at KMT2D were higher in BRCA2 d primary tumors, as was the total SNV frequency at KMT2D in BRCA2 d metastatic tumors. Homozygous deletions at NEK3, RB1, and APC were enriched in BRCA2 d primary tumors, and RB1 deletions in metastatic BRCA2 d tumors as well. TMPRSS2-ETV1 fusions were more common in BRCA2 d tumors. These results identify somatic alterations that hallmark etiological and prognostic differences between BRCA2 d and BRCA2 i prostate tumors.https://doi.org/10.1038/s41698-022-00284-6 |
| spellingShingle | Kevin H. Kensler Shakuntala Baichoo Shailja Pathania Timothy R. Rebbeck The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer npj Precision Oncology |
| title | The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer |
| title_full | The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer |
| title_fullStr | The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer |
| title_full_unstemmed | The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer |
| title_short | The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer |
| title_sort | tumor mutational landscape of brca2 deficient primary and metastatic prostate cancer |
| url | https://doi.org/10.1038/s41698-022-00284-6 |
| work_keys_str_mv | AT kevinhkensler thetumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT shakuntalabaichoo thetumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT shailjapathania thetumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT timothyrrebbeck thetumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT kevinhkensler tumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT shakuntalabaichoo tumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT shailjapathania tumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer AT timothyrrebbeck tumormutationallandscapeofbrca2deficientprimaryandmetastaticprostatecancer |