Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer
Hereditary breast cancer (BC) corresponds to 5% of all BC and a larger parcel of early-onset disease. The incorporation of next-generation sequencing (NGS) techniques reduced the cost of molecular testing and allowed the inclusion of additional cancer predisposition genes in panels that are more com...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.873395/full |
| _version_ | 1811345149811228672 |
|---|---|
| author | Thais Baccili Cury Megid Mateus C. Barros-Filho Janina Pontes Pisani Maria Isabel Achatz |
| author_facet | Thais Baccili Cury Megid Mateus C. Barros-Filho Janina Pontes Pisani Maria Isabel Achatz |
| author_sort | Thais Baccili Cury Megid |
| collection | DOAJ |
| description | Hereditary breast cancer (BC) corresponds to 5% of all BC and a larger parcel of early-onset disease. The incorporation of next-generation sequencing (NGS) techniques reduced the cost of molecular testing and allowed the inclusion of additional cancer predisposition genes in panels that are more comprehensive. This enabled the identification of germline pathogenic variants in carriers and the introduction of risk-reducing strategies. It also resulted in the identification of the co-occurrence of more than one germline pathogenic variant in BC genes in some families. This is a rare event, and there are few reports on its impact on cancer risk. We conducted a single-institution retrospective study in which 1,156 women with early onset BC and/or a family history of cancer were tested by a germline multi-gene hereditary cancer panel. Germline pathogenic variants in high- and/or moderate-penetrance BC genes were identified in 19.5% of the individuals (n = 226). The most frequent variants were found in TP53 (69 of 226; 55 of them represented by p.R337H), BRCA1 (47 of 226), and BRCA2 (41 of 226). Double heterozygous (DH) variants were detected in 14 cases, representing 1.2% of all individuals assessed. There were no significant differences in age of BC onset and risk for bilateral BC in DH carriers when compared with those with one germline variant. |
| first_indexed | 2024-04-13T19:58:43Z |
| format | Article |
| id | doaj.art-dce4e7c7ca874525878d7d57c3cc5d32 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T19:58:43Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-dce4e7c7ca874525878d7d57c3cc5d322022-12-22T02:32:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.873395873395Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancerThais Baccili Cury MegidMateus C. Barros-FilhoJanina Pontes PisaniMaria Isabel AchatzHereditary breast cancer (BC) corresponds to 5% of all BC and a larger parcel of early-onset disease. The incorporation of next-generation sequencing (NGS) techniques reduced the cost of molecular testing and allowed the inclusion of additional cancer predisposition genes in panels that are more comprehensive. This enabled the identification of germline pathogenic variants in carriers and the introduction of risk-reducing strategies. It also resulted in the identification of the co-occurrence of more than one germline pathogenic variant in BC genes in some families. This is a rare event, and there are few reports on its impact on cancer risk. We conducted a single-institution retrospective study in which 1,156 women with early onset BC and/or a family history of cancer were tested by a germline multi-gene hereditary cancer panel. Germline pathogenic variants in high- and/or moderate-penetrance BC genes were identified in 19.5% of the individuals (n = 226). The most frequent variants were found in TP53 (69 of 226; 55 of them represented by p.R337H), BRCA1 (47 of 226), and BRCA2 (41 of 226). Double heterozygous (DH) variants were detected in 14 cases, representing 1.2% of all individuals assessed. There were no significant differences in age of BC onset and risk for bilateral BC in DH carriers when compared with those with one germline variant.https://www.frontiersin.org/articles/10.3389/fonc.2022.873395/fullbreast cancerdouble heterozygous variantsgermline panelshereditary breast cancerNGS |
| spellingShingle | Thais Baccili Cury Megid Mateus C. Barros-Filho Janina Pontes Pisani Maria Isabel Achatz Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer Frontiers in Oncology breast cancer double heterozygous variants germline panels hereditary breast cancer NGS |
| title | Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer |
| title_full | Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer |
| title_fullStr | Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer |
| title_full_unstemmed | Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer |
| title_short | Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer |
| title_sort | double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer |
| topic | breast cancer double heterozygous variants germline panels hereditary breast cancer NGS |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.873395/full |
| work_keys_str_mv | AT thaisbaccilicurymegid doubleheterozygouspathogenicvariantsprevalenceinacohortofpatientswithhereditarybreastcancer AT mateuscbarrosfilho doubleheterozygouspathogenicvariantsprevalenceinacohortofpatientswithhereditarybreastcancer AT janinapontespisani doubleheterozygouspathogenicvariantsprevalenceinacohortofpatientswithhereditarybreastcancer AT mariaisabelachatz doubleheterozygouspathogenicvariantsprevalenceinacohortofpatientswithhereditarybreastcancer |