Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment
<i>BRCA1</i>/<i>2</i> are tumor suppressor genes involved in DNA double-strand break repair. They are the most penetrant genes for hereditary breast and ovarian cancers, but pathogenic variants in these two genes can be identified only in a fraction of hereditary cases. Follo...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/4/682 |
| _version_ | 1797434628980604928 |
|---|---|
| author | Angela Secondino Flavio Starnone Iolanda Veneruso Maria Antonietta Di Tella Serena Conato Carmine De Angelis Sabino De Placido Valeria D’Argenio |
| author_facet | Angela Secondino Flavio Starnone Iolanda Veneruso Maria Antonietta Di Tella Serena Conato Carmine De Angelis Sabino De Placido Valeria D’Argenio |
| author_sort | Angela Secondino |
| collection | DOAJ |
| description | <i>BRCA1</i>/<i>2</i> are tumor suppressor genes involved in DNA double-strand break repair. They are the most penetrant genes for hereditary breast and ovarian cancers, but pathogenic variants in these two genes can be identified only in a fraction of hereditary cases. Following the diffusion of <i>BRCA</i> molecular testing and the availability of specific therapeutic strategies for the management of pathogenic variant carriers, the demand for the analysis of additional predisposing genetic factors has increased. Indeed, there is accumulating evidence regarding the role of other genes, including <i>CHEK2</i> and <i>PALB2.</i> Both of them are involved in the same molecular pathway as <i>BRCA</i> genes, with <i>CHEK2</i> being responsible for cell cycle stopping to allow the repair of DNA double-strand breaks and <i>PALB2</i> being able to interact with <i>BRCA1</i> and activate <i>BRCA2</i>. Thus, their role as additional hereditary cancer predisposing factors is intriguing. Accordingly, guidelines for hereditary cancer risk assessment have been updated to include the criteria for additional genes testing. In this context, we validated a commercially available kit allowing for the simultaneous analysis of <i>BRCA1</i>, <i>BRCA2</i>, <i>CHEK2</i> and <i>PALB2</i>. Forty-eight patients, already tested for <i>BRCA</i> mutational status, were re-analyzed in the present study. Results comparison showed that the tested method was able to correctly identify all the variants previously detected in the same patients. In particular, all single-nucleotide variants and small indels were correctly identified. Moreover, two copy number variants, included to assess the software’s performance in detecting this kind of gene alteration, were also detected. Even if copy number variant estimation still requires confirmation by a molecular technique to avoid false positive results, it is able to reduce the number of patients requiring multiplex ligation probe amplification analysis, positively impacting the test’s turnaround time. Finally, since the time and costs of the analysis are similar to those required just for <i>BRCA</i> genes, this strategy may be affordable for providing a more comprehensive test for hereditary cancer risk assessment. |
| first_indexed | 2024-03-09T10:34:46Z |
| format | Article |
| id | doaj.art-0e624c92dca040a197df8e4d6ba53ff3 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T10:34:46Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0e624c92dca040a197df8e4d6ba53ff32023-12-01T20:57:29ZengMDPI AGGenes2073-44252022-04-0113468210.3390/genes13040682Evaluation of a Four-Gene Panel for Hereditary Cancer Risk AssessmentAngela Secondino0Flavio Starnone1Iolanda Veneruso2Maria Antonietta Di Tella3Serena Conato4Carmine De Angelis5Sabino De Placido6Valeria D’Argenio7Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Napoli, ItalyCEINGE-Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Napoli, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Napoli, ItalyCEINGE-Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Napoli, ItalyCEINGE-Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Napoli, ItalyDepartment of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Napoli, ItalyDepartment of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 80131 Napoli, ItalyCEINGE-Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Napoli, Italy<i>BRCA1</i>/<i>2</i> are tumor suppressor genes involved in DNA double-strand break repair. They are the most penetrant genes for hereditary breast and ovarian cancers, but pathogenic variants in these two genes can be identified only in a fraction of hereditary cases. Following the diffusion of <i>BRCA</i> molecular testing and the availability of specific therapeutic strategies for the management of pathogenic variant carriers, the demand for the analysis of additional predisposing genetic factors has increased. Indeed, there is accumulating evidence regarding the role of other genes, including <i>CHEK2</i> and <i>PALB2.</i> Both of them are involved in the same molecular pathway as <i>BRCA</i> genes, with <i>CHEK2</i> being responsible for cell cycle stopping to allow the repair of DNA double-strand breaks and <i>PALB2</i> being able to interact with <i>BRCA1</i> and activate <i>BRCA2</i>. Thus, their role as additional hereditary cancer predisposing factors is intriguing. Accordingly, guidelines for hereditary cancer risk assessment have been updated to include the criteria for additional genes testing. In this context, we validated a commercially available kit allowing for the simultaneous analysis of <i>BRCA1</i>, <i>BRCA2</i>, <i>CHEK2</i> and <i>PALB2</i>. Forty-eight patients, already tested for <i>BRCA</i> mutational status, were re-analyzed in the present study. Results comparison showed that the tested method was able to correctly identify all the variants previously detected in the same patients. In particular, all single-nucleotide variants and small indels were correctly identified. Moreover, two copy number variants, included to assess the software’s performance in detecting this kind of gene alteration, were also detected. Even if copy number variant estimation still requires confirmation by a molecular technique to avoid false positive results, it is able to reduce the number of patients requiring multiplex ligation probe amplification analysis, positively impacting the test’s turnaround time. Finally, since the time and costs of the analysis are similar to those required just for <i>BRCA</i> genes, this strategy may be affordable for providing a more comprehensive test for hereditary cancer risk assessment.https://www.mdpi.com/2073-4425/13/4/682breast cancerovarian cancer<i>BRCA1</i><i>BRCA2</i><i>CHEK2</i><i>PALB2</i> |
| spellingShingle | Angela Secondino Flavio Starnone Iolanda Veneruso Maria Antonietta Di Tella Serena Conato Carmine De Angelis Sabino De Placido Valeria D’Argenio Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment Genes breast cancer ovarian cancer <i>BRCA1</i> <i>BRCA2</i> <i>CHEK2</i> <i>PALB2</i> |
| title | Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment |
| title_full | Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment |
| title_fullStr | Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment |
| title_full_unstemmed | Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment |
| title_short | Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment |
| title_sort | evaluation of a four gene panel for hereditary cancer risk assessment |
| topic | breast cancer ovarian cancer <i>BRCA1</i> <i>BRCA2</i> <i>CHEK2</i> <i>PALB2</i> |
| url | https://www.mdpi.com/2073-4425/13/4/682 |
| work_keys_str_mv | AT angelasecondino evaluationofafourgenepanelforhereditarycancerriskassessment AT flaviostarnone evaluationofafourgenepanelforhereditarycancerriskassessment AT iolandaveneruso evaluationofafourgenepanelforhereditarycancerriskassessment AT mariaantoniettaditella evaluationofafourgenepanelforhereditarycancerriskassessment AT serenaconato evaluationofafourgenepanelforhereditarycancerriskassessment AT carminedeangelis evaluationofafourgenepanelforhereditarycancerriskassessment AT sabinodeplacido evaluationofafourgenepanelforhereditarycancerriskassessment AT valeriadargenio evaluationofafourgenepanelforhereditarycancerriskassessment |